2023, 松田嘉博先生記念学術奨学金, Yoshihiro Matsuda Memorial Academic Award　　　　　　　　　　　　　　　

Jan. 2019, 北海道整形災害外科学会 学術奨励賞, 北海道整形災害外科学会 Society award　　　　　　　　　　　　　　　
Alaa Terkawi

Mar. 2018, 第37回北海道大学大学院医学研究院・大学院医学院, 医学部医学科高桑榮松奨学基金奨励賞　　　　　　　　　　　　　　　
Alaa Terkawi

Mar. 2017, 日本学術振興会 Travel Fellowship Award for the Japan-Brazil Malaria Research Workshop, Travel Fellowship Award for the Japan-Brazil Malaria Research Workshop　　　　　　　　　　　　　　　
Alaa Terkawi

Nov. 2009, 日本学術振興会外国人特別研究員, JSPS fellowship　　　　　　　　　　　　　　　
Alaa Terkawi

Efferocytosis at the frontline of homeostasis: Shaping the bone microenvironment and therapeutic implications in related diseases
Liyile Chen, Ken Kadoya, Endo Tsutomu, Norimasa Iwasaki, M Alaa Terkawi
Cytokine & Growth Factor Reviews, Elsevier BV, May 2025, [Peer-reviewed], [Lead author, Last author, Corresponding author]
Scientific journal

Impact of different dosages of e-beam irradiation on mechanical strength of vitamin E-blended ultra-high-molecular-weight polyethylene and the osteolytic activities of its wear debris
Junki Shiota, Daisuke Takahashi, Liyile Chen, Shunichi Yokota, Tomoyo Yutani, Hend Alhasan, Tsutomu Endo, Tomohiro Sugimoto, Keita Uetsuki, M Alaa Terkawi, Norimasa Iwasaki
Materialia, 39, 102345, 102345, Elsevier BV, Mar. 2025, [Corresponding author]
Scientific journal

Intra-Articular Administration of Ganglioside Sugars Protects Cartilage from Progressive Degeneration in an Instability OA Rabbit Model.
Masanari Hamasaki, Tomohiro Onodera, Junichi Furukawa, Masahiro Todoh, Yuma Sakai, Taku Ebata, Mohamad Alaa Terkawi, Kentaro Homan, Norimasa Iwasaki
Cartilage, 19476035241311542, 19476035241311542, 14 Jan. 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease that has no cure, and current therapies are intended to minimize pain. There is, therefore, a need for effective pharmacologic agents that reverse or slow the progression of joint damage. We report herein on an investigation of the effects of intra-articular injections of ganglioside sugars on the progression of OA in an experimental rabbit model. DESIGN: Knee OA was induced Japanese in White rabbits by anterior cruciate ligament transection (ACLT). Ganglioside sugars at concentrations of 0.1, 0.3, and 0.9 mg/ml were then intra-articularly injected as a possible treatment for OA. Controls received intra-articular injections of saline. Knees were assessed macroscopically, histologically, and mechanically at 13 weeks after ACLT induction. RESULTS: Macroscopically, knees of the groups that received ganglioside sugars at concentrations of 0.3 and 0.9 mg/ml exhibited milder cartilage degradation compared to the controls. Consistent with these results, histological scores for these knees were significantly higher than the corresponding values for the control knees. Lectin histochemistry staining revealed that the treatment with ganglioside sugars at concentrations of 0.3 and 0.9 mg/ml was associated with a remarkable increase in the levels of GalNAc-positive chondrocytes in cartilage. Coefficient of friction testing also demonstrated that cartilages treated with ganglioside sugars had a lower coefficient of frictions than the values for the control group. CONCLUSIONS: Intra-articular injections of ganglioside sugars prevented cartilage degeneration in an OA-instability model. These results highlight the promising therapeutic potential for using ganglioside sugars in the treatment of progressive OA.

Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris
Takuya Ogawa, Shunichi Yokota, Liyile Chen, Yuki Ogawa, Yoshio Nishida, Taiki Tokuhiro, Hend Alhasan, Tomoyo Yutani, Tomohiro Shimizu, Daisuke Takahashi, Takuji Miyazaki, Tsutomu Endo, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Biomedicines, 13, 1, 170, 170, MDPI AG, 13 Jan. 2025, [Corresponding author]
Scientific journal, Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model. Methods: Inverted cell culture model was used for stimulating the cells with wear debris in vitro, and calvarial osteolysis model was used for evaluating the therapeutic effects of inhibitors in vivo. Results: The immunostaining of periprosthetic bone tissues demonstrated a number of osteocytes expressing ferroptosis markers. Likewise, the expressions of ferroptosis markers were confirmed in polyethylene-wear-debris-stimulated osteocyte-like cells and primary osteoblasts in a direct stimulation model but not in an indirect stimulation model. Furthermore, polyethylene wear debris was implanted onto calvarial bone and mice were treated with the ferroptosis inhibitors DFO and Fer-1. These treatments alleviated the inflammatory and pathological bone resorption induced by the wear debris implantation. Conclusions: Our data broaden the knowledge of the pathogenesis of periprosthetic osteolysis and highlight ferroptosis as a promising therapeutic target.

Visceral fat obesity predicts ossification of the posterior longitudinal ligament: annual health examination data-based evidence
Soya Miura, Yoshinao Koike, Tsutomu Endo, Masahiko Takahata, Hideki Sudo, Ken Kadoya, Masahiro Kanayama, Ryo Fujita, Shotaro Fukada, M Alaa Terkawi, Katsuhisa Yamada, Takashi Ohnishi, Daisuke Ukeba, Hiroyuki Tachi, Yuichi Hasegawa, Misaki Ishii, Norimasa Iwasaki
The Spine Journal, Elsevier BV, Jan. 2025
Scientific journal

Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint
Taiki Tokuhiro, Gen Matsumae, Tsutomu Endo, Yuki Ogawa, Takuya Ogawa, Chen Liyile, Yoshio Nishida, Hend Alhasan, Hideyuki Kobayashi, Taku Ebata, Tomohiro Shimizu, Daisuke Takahashi, Tomohiro Onodera, Ken Kadoya, Alaa Terkawi, Norimasa Iwasaki
Journal of Autoimmunity, Dec. 2024, [Corresponding author]
English, Scientific journal

Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage.
Keita Kitahara, Taku Ebata, Chen Liyile, Yoshio Nishida, Yuki Ogawa, Taiki Tokuhiro, Junki Shiota, Tatsuya Nagano, Taichi E Takasuka, Tsutomu Endo, Tomohiro Shimizu, Hend Alhasan, Tsuyoshi Asano, Daisuke Takahashi, Kentaro Homan, Tomohiro Onodera, Ken Kadoya, M Alaa Terkawi, Norimasa Iwasaki
Cell communication and signaling : CCS, 22, 1, 569, 569, 27 Nov. 2024, [Corresponding author], [International Magazine]
English, Scientific journal, BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease characterized by cartilage degradation and various degrees of inflammation in the synovium. Growing evidence highlights that neutrophil extracellular vesicles (EVs) play a protective role in arthritic joints by promoting the resolution of inflammation and the synthesis of proteoglycans in cartilage. However, this homeostatic function is dependent on the activation state of neutrophils and the surrounding environment/tissues. Hence, we explored the chondroprotective functions of neutrophil-derived EVs under different stimulation conditions and the underlying molecular mechanism. METHODS: Human blood-derived neutrophils, murine bone marrow-derived neutrophils, C-28I2 cells and primary chondrocytes were used. Neutrophils were stimulated with different cytokines, and their EVs were isolated for chondrocyte stimulation and further subjected to RNA-sequencing analysis. Two experimental murine OA models were used, and the treatment was performed by intraarticular injections. RESULTS: Conditioned medium from neutrophils stimulated with TGF-β (N-β) had the greatest inhibitory effect on the expression of catabolic factors in stimulated chondrocytes. These protective effects were not impaired when conditioned medium of N-β from AnxA1-deficient mice was used. Consistent with these results, EVs isolated from N-β significantly reduced the expression of catabolic factors in stimulated chondrocytes. Bulk RNA-seq analysis revealed that secreted frizzled-related protein 5 (SFRP5) is upregulated in N-β-EV-stimulated chondrocytes. Furthermore, recombinant SFRP5 treatment significantly reduced the expression of catabolic factors in vitro and catabolic process in experimental murine OA models. CONCLUSIONS: The current study emphasizes the potential therapeutic application of neutrophils in OA and provides new knowledge on the molecular mechanisms underlying their function.

Associations between glycan signature alterations and the cellular antigenic properties of passaged chondrocytes
Kentaro Homan, Taiki Tokuhiro, Tomohiro Onodera, Hisatoshi Hanamatsu, Jun-ichi Furukawa, Taku Ebata, Masatake Matsuoka, Ken Kadoya, M. Alaa Terkawi, Norimasa Iwasaki
Frontiers in Immunology, 15, Frontiers Media SA, 25 Nov. 2024, [Corresponding author]
Scientific journal, Background

Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles.

Objective

This study investigated the impact of chondrocyte passaging on glycan profiles and their antigenic properties. We hypothesized that alterations in glycan composition due to passaging may contribute to the enhanced ability to activate macrophages, thereby affecting the outcome of cell transplantation therapy.

Methods

Peritoneal macrophages and primary articular chondrocytes were isolated from C57BL/6 mice to establish direct and indirect coculture models. Macrophage activation was assessed by measuring the concentrations of IL-6 and nitric oxide in the culture supernatants or their gene expression. Glycome analysis of various glycoconjugates was performed by glycoblotting methods combined with the SALSA procedure for N-glycans and GSLs and the BEP method for O-glycans.

Results

Our results revealed that direct coculture of macrophages with passaged chondrocytes increased the production of proinflammatory cytokines, including IL-6 and NO, as the number of passages increased. With increasing passage number, the expression of GD3 substantially decreased, and the expression of GM3, especially GD1a, significantly increased. Coculturing passaged GM3S knockout chondrocytes with macrophages significantly suppressed IL-6 expression, implying reduced macrophage activation.

Conclusion

The observed activation of macrophages due to alterations in the glycan profile of chondrocytes provides a possible explanation for the antigenicity and immune rejection of transplanted cells.

Dynamic transcriptome analysis of osteal macrophages identifies distinct subset with senescence features in experimental osteoporosis.
Yoshio Nishida, M Alaa Terkawi, Gen Matsumae, Shunichi Yokota, Taiki Tokuhiro, Yuki Ogawa, Hotaka Ishizu, Junki Shiota, Tsutomu Endo, Hend Alhasan, Taku Ebata, Keita Kitahara, Tomohiro Shimizu, Daisuke Takahashi, Masahiko Takahata, Ken Kadoya, Norimasa Iwasaki
JCI insight, 31 Oct. 2024, [Corresponding author], [International Magazine]
English, Scientific journal, Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence and apoptotic process. A scRNA-seq analysis revealed that osteal macrophages were heterogenously clustered into 6 subsets that expressed proliferative, inflammatory, anti-inflammatory and efferocytosis gene signatures. Importantly, postmenopausal mice exhibited a 20-fold increase in subset-3 that showed a typical gene signature of cell senescence and inflammation. These findings suggest that the decreased production of estrogen due to postmenopause altered the osteal macrophages subsets, resulting in a shift toward cell senescence and inflammatory conditions in the bone microenvironment. Furthermore, adoptive macrophage transfer onto calvarial bone was performed and mice that received oxidative-stressed macrophages exhibited greater osteolytic lesions than control macrophages, suggesting the role of these cells in development of inflammaging in bone microenvironment. Consistently, depletion of senescent cells and oxidative-stressed macrophages subset alleviated the excessive bone loss in postmenopausal mice. Our data provided a new insight into the pathogenesis of osteoporosis and sheds light on a new therapeutic approach for the treatment/prevention of postmenopausal osteoporosis.

継代培養に伴う糖鎖抗原の変化と自家細胞における免疫応答の発現
宝満 健太郎, 徳廣 泰貴, 小野寺 智洋, 花松 久寿, 古川 潤一, 江畑 拓, Terkawi Alaa, 松岡 正剛, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 98, 8, S1844, S1844, (公社)日本整形外科学会, Sep. 2024
Japanese

Midterm Results of Severe Hip Dysplasia after Using a Cementless Acetabular Component with Bulk Bone Graft in Total Hip Arthroplasty: A Minimum Five-Year Follow-Up Study.
Takuya Konno, Tomohiro Shimizu, Masahiro Inoue, Takeshi Masuda, Mohamad Alaa Terkawi, Norimasa Iwasaki, Daisuke Takahashi
Bioengineering (Basel, Switzerland), 11, 8, 19 Aug. 2024, [International Magazine]
English, Scientific journal, In patients with severe hip dysplasia, total hip arthroplasty (THA) using bulk bone graft (BBG) enhances anatomic cup positioning and provides early structural support. This study assesses the mid-term outcomes of THA with BBG in patients with over 50% graft bone coverage. Among 1951 patients who underwent THA between 2003 and 2007, 183 had BBG. After excluding early dropouts and infections, 151 patients remained. They were classified into uncovered (<50% coverage, 79 patients) and covered (>50% coverage, 72 patients) groups. The efficacy of cup fixation was compared between these groups. After ten years, the survival rate for not needing THA revision was 98% in the uncovered group and 100% in the covered group, while the rate for radiographic stability was 93% versus 99%, respectively. Although the cutoff value for the uncovered portion could not be clarified in this study, the mid-term results for 50% to approximately 70% uncovered were comparable to those for 50% or lesser, which have previously been expected to perform well. Recently, biomechanically advantageous bone grafting techniques have been identified, and based on the results of this study, it may be possible to expand the indications for THA with bone grafting for developmental dysplasia of the hip.

Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.
Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Ryo Fujita, Daisuke Yoneoka, Masahiro Kanayama, Ken Kadoya, Tomoka Hasegawa, Mohamad Alaa Terkawi, Katsuhisa Yamada, Hideki Sudo, Taku Ebata, Misaki Ishii, Norimasa Iwasaki
Journal of bone and mineral metabolism, 08 Jun. 2024, [Domestic magazines]
English, Scientific journal, INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor.
Hideyuki Kobayashi, M Alaa Terkawi, Masahiro Ota, Tomoka Hasegawa, Tomomaya Yamamoto, Tomohiro Shimizu, Dai Sato, Ryo Fujita, Toshifumi Murakami, Norio Amizuka, Norimasa Iwasaki, Masahiko Takahata
Bone research, 12, 1, 35, 35, 07 Jun. 2024, [International Magazine]
English, Scientific journal, DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5 A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in Trem-2, Clec5a, Siglec-15 were generated. In addition, mice double deficient in these DAR genes and FcεRI gamma chain (FcR)γ, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably, Siglec-15 deficient mice and Siglec-15/FcRγ double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from Siglec-15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.

継代細胞における糖鎖シグネチャーの解明
宝満 健太郎, 徳廣 泰貴, 小野寺 智洋, 江畑 拓, Alaa Terkawi, 松岡 正剛, 花松 久寿, 古川 潤一, 角家 健, 岩崎 倫政
北海道整形災害外科学会雑誌, 66, 143rd suppl, 85, 85, 北海道整形災害外科学会, 2024
Japanese

Molecular and Cellular Mechanisms of Bone and Cartilage Diseases
M. Alaa Terkawi
Biomedicines, 08 Sep. 2023, [Corresponding author]
Scientific journal

High whole-body bone mineral density in ossification of the posterior longitudinal ligament.
Ryo Fujita, Tsutomu Endo, Masahiko Takahata, Yoshinao Koike, Daisuke Yoneoka, Ryota Suzuki, Masaru Tanaka, Katsuhisa Yamada, Hideki Sudo, Tomoka Hasegawa, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 23, 10, 1461, 1470, 10 Jul. 2023, [International Magazine]
English, Scientific journal, BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.

Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.
Shotaro Fukada, Tsutomu Endo, Masahiko Takahata, Masahiro Kanayama, Yoshinao Koike, Ryo Fujita, Ryota Suzuki, Toshifumi Murakami, Tomoka Hasegawa, Mohamad Alaa Terkawi, Tomoyuki Hashimoto, Kastuhisa Yamada, Hideki Sudo, Ken Kadoya, Norimasa Iwasaki
The spine journal : official journal of the North American Spine Society, 23, 9, 1287, 1295, 07 May 2023, [International Magazine]
English, Scientific journal, BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.

Macrophage‐derived extracellular vesicles trigger non‐canonical pyroptosis in chondrocytes leading to cartilage catabolism in osteoarthritis
Taku Ebata, Mohamad Alaa Terkawi, Keita Kitahara, Syunichi Yokota, Junki Shiota, Yoshio Nishida, Gen Matsumae, Hend Alhasan, Masanari Hamasaki, Kazutoshi Hontani, Tomohiro Shimizu, Daisuke Takahashi, Tsutomu Endo, Tomohiro Onodera, Ken Kadoya, Norimasa Iwasaki
Arthritis & Rheumatology, 16 Mar. 2023, [Corresponding author], [International Magazine]
English, Scientific journal, OBJECTIVES: The severity of osteoarthritis and cartilage degeneration are highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. Here, we explored the pathological role of inflammatory macrophage extracellular vesicles in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages and the resulting extracellular vesicles were harvested for chondrocyte stimulation in vitro and intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-seq analysis and other functional assays. The action of caspase-11 was disrupted in vitro using a specific siRNA or wedelolactone, and in experimental OA-murine models by the intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-seq analyses of stimulated chondrocytes indicated that upregulated genes are mainly categorized into apoptotic process and TNF-signaling pathway which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase-11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and the pathological changes in collagenase-and joint instability-induced OA models. CONCLUSIONS: Our results provide a new insight into the pathological mechanisms of OA and suggest that non-canonical pyroptosis in chondrocytes represents an attractive therapeutic target for future treatment.

Comparison of re-revision rate and radiological outcomes between Kerboull-type plate and metal mesh with impaction bone grafting for revision total hip arthroplasty.
Hotaka Ishizu, Tomohiro Shimizu, Fumio Sasazawa, Daisuke Takahashi, Mohamad Alaa Terkawi, Kaname Takahashi, Yusuke Ohashi, Masahiro Kanayama, Norimasa Iwasaki
BMC musculoskeletal disorders, 24, 1, 134, 134, 20 Feb. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: This study compared the re-revision rate and radiographic outcomes of revision total hip arthroplasty (THA) using a Kerboull-type acetabular reinforcement device (KT plate) with bulk structural allograft and metal mesh with impaction bone grafting (IBG). METHODS: Ninety-one hips of 81 patients underwent revision THA for American Academy of Orthopedic Surgeons (AAOS) classification type III defects from 2008 to 2018. Of these, seven hips of five patients and 15 hips of 13 patients were excluded due to insufficient follow-up information (< 24 months) and large bone defects with a vertical defect height ≥ 60 mm, respectively. The current study compared the survival and radiographic parameters of 45 hips of 41 patients using a KT plate (KT group) and 24 hips of 24 patients using a metal mesh with IBG (mesh group). RESULTS: Eleven hips (24.4%) in the KT group and 1 hip (4.2%) in the mesh group exhibited radiological failure. Moreover, 8 hips in the KT group (17.0%) required a re-revision THA, while none of the patients in the mesh group required a re-revision. The survival rate with radiographic failure as the endpoint in the mesh group was significantly higher than that in the KT group (100% vs 86.7% at 1-year and 95.8% vs 80.0% at 5-years, respectively; p = 0.032). On multivariable analysis evaluating factors associated with radiographic failure, there were no significant associations with any radiographic measurement. Of the 11 hips with radiographic failure, 1 (11.1%), 3 (12.5%), and 7 (58.3%) hips were of Kawanabe classification stages 2, 3, and 4, respectively. CONCLUSIONS: The findings of this study suggest that revision THA using KT plates with bulk structure allografts could provide poorer clinical outcomes than revision THA using a metal mesh with IBG. Although revision THA using KT plates with bulk structural allografts could set the true hip center, there is no association between a high hip center and clinical outcomes. The relationship between the position of the KT plate and the host bone might be considered more carefully.

Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.
Kazuha Nakabachi, Tsutomu Endo, Masahiko Takahata, Ryo Fujita, Yoshinao Koike, Ryota Suzuki, Yuichi Hasegawa, Toshifumi Murakami, Katsuhisa Yamada, Hideki Sudo, Mohamad Alaa Terkawi, Ken Kadoya, Norimasa Iwasaki
Scientific reports, 13, 1, 638, 638, 12 Jan. 2023, [International Magazine]
English, Scientific journal, Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.

Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma.
Yasuhiro Yamamoto, Ken Kadoya, Mohamad Alaa Terkawi, Takeshi Endo, Kohtarou Konno, Masahiko Watanabe, Satoshi Ichihara, Akira Hara, Kazuo Kaneko, Norimasa Iwasaki, Muneaki Ishijima
Life science alliance, 5, 10, Oct. 2022, [International Magazine]
English, Scientific journal, Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration.

Inhibitory role of Annexin A1 in pathological bone resorption and its therapeutic implications in periprosthetic osteolysis
Alhasan H, Terkawi MA, Matumae G, Ebata T, Tian Y, Shimizu T, Nishida Y, Yokota S, Garcia-Martin F, Abd Elwakil MM, Takahashi D, Younis MA, Harashima H, Kadoya K, Iwasaki N
Nature Communications, 13, 1, 3919, 3919, Jun. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.

Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention
M Alaa Terkawi, Taku Ebata, Shunichi Yokota, Daisuke Takahashi, Tsutomu Endo, Gen Matsumae, Tomohiro Shimizu, Ken Kadoya, Norimasa Iwasaki
Biomedicines, 10, 5, 10 May 2022, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.

IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.
Alaa Terkawi
Cellular and molecular life sciences : CMLS, 79, 6, 289, 289, 10 May 2022, [International Magazine]
English, Scientific journal, Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.

Finite Element Analysis of Optimal Positioning of Femoral Osteotomy in Total Hip Arthroplasty With Subtrochanteric Shortening.
Daisuke Takahashi, Yoshihiro Noyama, Tomohiro Shimizu, Mohamad Alaa Terkawi, Norimasa Iwasaki
Arthroplasty today, 14, 105, 109, Apr. 2022, [International Magazine]
English, Scientific journal, Background: Total hip arthroplasty with femoral shortening is frequently recommended for patients with high hip dislocation. However, the possibility of postoperative rotational deviation of the stem presents a challenge for surgeons. We aimed to determine the optimal position for osteotomy in total hip arthroplasty under full weight-bearing and turning torque by using finite element analysis. Methods: Four models of femoral osteotomy with 30-mm transverse shortening at 30% (model 30), 40% (model 40), 50% (model 50), and 60% (model 60) from the proximal end of the full length of the Exeter stem were constructed. Using finite element analysis, the constructs were first analyzed under an axial load of 1500 N and then with an added torsional load of 10°. Results: The analyses under torsional loading conditions revealed that the maximum von Mises stress on the stem in each model occurred at the proximal end of the distal fragment and the distal side of the stem. The maximum stress values at the stem were 819 MPa (model 30), 825 MPa (model 40), 916 MPa (model 50), and 944 MPa (model 60). The maximum stress values at the osteotomy site of the medullary cavity side of the distal bone fragment were 761 MPa (model 30), 165 MPa (model 40), 187 MPa (model 50), and 414 MPa (model 60). Conclusions: The osteotomy level should be around the proximal 40% of the full length of the Exeter stem, which is most suitable for rotation stability in the early postoperative period.

Inflammasome activation in the hip synovium of rapidly destructive coxopathy patients and its relationship with the development of synovitis and bone loss
Shunichi Yokota, Tomohiro Shimizu, Gen Matsumae, Taku Ebata, Hend Alhasan, Daisuke Takahashi, Mohamad Alaa Terkawi, Norimasa Iwasaki
The American Journal of Pathology, 192, 5, 794, 804, Elsevier BV, Mar. 2022, [Corresponding author], [International Magazine]
English, Scientific journal, Rapidly destructive coxopathy (RDC), a rare disease of unknown etiology, is characterized by the rapid destruction of the hip joint. In the current study, the potential involvement of inflammasome signaling in the progression of RDC was investigated. Histopathologic changes and the gene expression of inflammasome activation markers in hip synovial tissues collected from patients with RDC were evaluated and compared with those of osteoarthritis and osteonecrosis of the femoral head patients. The synovial tissues of patients with RDC exhibited remarkable increases in the number of infiltrated macrophages and osteoclasts, and the expression of inflammasome activation markers was also increased compared with those of osteoarthritis and osteonecrosis of the femoral head patients. To further understand the histopathologic changes in the joint, a co-culture model of macrophages and synoviocytes that mimicked the joint environment was developed. Remarkably, the gene expression levels of NLRP3, GSDMD, IL1B, TNFA, ADMTS4, ADMTS5, MMP3, MMP9, and RANKL were significantly elevated in the synoviocytes that were co-cultured with activated THP-1 macrophages, suggesting the association between synovitis and inflammasome activation. Consistent with these findings, osteoclast precursor cells that were co-cultured with stimulated synoviocytes exhibited an increased number of tartrate-resistant acid phosphatase-positive cells, compared with cells that were co-cultured with non-stimulated synoviocytes. These findings suggest that the activation of inflammasome signaling in the synovium results in an increase in local inflammation and osteoclastogenesis, thus leading to the rapid bone destruction in RDC.

Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives
M A Terkawi, G Matsumae, T Shimizu, D Takahashi, K Kadoya, N Iwasaki
Int. J. Mol. Sci. 2022, 23(3), 1786; https://doi.org/10.3390/ijms23031786, 23, 3, Feb. 2022, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints, protection of vital organs and storage of minerals. Bone is a metabolically active organ that undergoes continuous remodeling processes to maintain its architecture, shape, and function throughout life. One of the most important medical discoveries of recent decades has been that the immune system is involved in bone remodeling. Indeed, chronic inflammation has been recognized as the most significant factor influencing bone homeostasis, causing a shift in the bone remodeling process toward pathological bone resorption. Bone osteolytic diseases typified by excessive bone resorption account for one of the greatest causes of disability worldwide, with significant economic and public health burdens. From this perspective, we discuss the recent findings and discoveries highlighting the cellular and molecular mechanisms that regulate this process in the bone microenvironment, in addition to the current therapeutic strategies for the treatment of osteolytic bone diseases.

Mature but not developing Schwann cells promote axon regeneration after peripheral nerve injury.
Alaa Terkawi
NPJ Regenerative medicine, 28 Jan. 2022, [Peer-reviewed]
Scientific journal, Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.

Evaluation of biological responses to micro-particles derived from a double network hydrogel
Gen Matsumae, Alaa Terkawi, Takayuki Nonoyama, Takayuki Kurokawa, Daisuke Takahashi, Tomohiro Shimizu, Ken Kadoya, Jian Ping Gong, Kazunori Yasuda, Norimasa Iwasaki
Biomaterials Science, Royal Society of Chemistry ({RSC}), 2022, [Corresponding author]
English, Scientific journal, The double network hydrogels (DN gels) composed of poly (2-acrylamido-2-methyl propanesulfonic acid) (PAMPS) as the brittle first network and poly (N,N-dimethylacrylamide) (PDMA) as the ductile second network have been proven...

Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris
Matsumae G, Kida H, Takahashi D, Shimizu T, Ebata T, Yokota S, Alhasan H, Aly MK, Yutani T, Uetsuki K, Terkawi MA, Iwasaki N
Journal of Biomedical Materials Research: Part B - Applied Biomaterials. Accepted, 110, 7, 1587, 1593, Jan. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant.

末梢神経損傷後早期免疫反応の詳細 好中球由来MIFによる修復機転の阻害
山本 康弘, 角家 健, 市原 理司, 原 章, Terkawi Alaa, 今野 幸太郎, 渡辺 雅彦, 岩崎 倫政, 金子 和夫, 石島 旨章
末梢神経, 32, 2, 268, 268, 日本末梢神経学会, Dec. 2021
Japanese

炎症性マクロファージ由来細胞外小胞を介した軟骨変性メカニズムの解明
江畑 拓, Terkawi Alaa, 松前 元, 横田 隼一, Alhasan Hend, 清水 智弘, 高橋 大介, 本谷 和俊, 小野寺 智洋, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1520, S1520, (公社)日本整形外科学会, Aug. 2021
Japanese

関節リウマチの局所骨溶解に関与するCCN3の機能解析
松前 元, Alaa Terkawi, 江畑 拓, Hend Alhasan, 横田 隼一, 清水 智弘, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1649, S1649, (公社)日本整形外科学会, Aug. 2021
Japanese

急速破壊型股関節症の滑膜におけるインフラマソームの活性化 病態解明の研究
横田 隼一, 清水 智弘, 松前 元, 江畑 拓, Hend Alhasan, 高橋 大介, Alaa Terkawi, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1653, S1653, (公社)日本整形外科学会, Aug. 2021
Japanese

PPARγシグナルを介した炎症性骨溶解制御におけるアネキシンA1(AnxA1)の機能解析
Hend Alhasan, 松前 元, 江畑 拓, 横田 隼一, 清水 智弘, 高橋 大介, Alaa Terkawi, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1700, S1700, (公社)日本整形外科学会, Aug. 2021
Japanese

炎症性マクロファージ由来細胞外小胞を介した軟骨変性メカニズムの解明
江畑 拓, Terkawi Alaa, 松前 元, 横田 隼一, Alhasan Hend, 清水 智弘, 高橋 大介, 本谷 和俊, 小野寺 智洋, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1520, S1520, (公社)日本整形外科学会, Aug. 2021
Japanese

関節リウマチの局所骨溶解に関与するCCN3の機能解析
松前 元, Alaa Terkawi, 江畑 拓, Hend Alhasan, 横田 隼一, 清水 智弘, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1649, S1649, (公社)日本整形外科学会, Aug. 2021
Japanese

急速破壊型股関節症の滑膜におけるインフラマソームの活性化 病態解明の研究
横田 隼一, 清水 智弘, 松前 元, 江畑 拓, Hend Alhasan, 高橋 大介, Alaa Terkawi, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1653, S1653, (公社)日本整形外科学会, Aug. 2021
Japanese

PPARγシグナルを介した炎症性骨溶解制御におけるアネキシンA1(AnxA1)の機能解析
Hend Alhasan, 松前 元, 江畑 拓, 横田 隼一, 清水 智弘, 高橋 大介, Alaa Terkawi, 岩崎 倫政
日本整形外科学会雑誌, 95, 8, S1700, S1700, (公社)日本整形外科学会, Aug. 2021
Japanese

Cardiotrophin like cytokine factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway
Shunichi Yokota, Gen Matsumae, Tomohiro Shimizu, Tomoka Hasegawa, Taku Ebata, Daisuke Takahashi, Cai Heguo, Yuan Tian, Hend Alhasan, Masahiko Takahata, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Bone, 153, 116140, 116140, Elsevier {BV}, Aug. 2021, [Corresponding author], [International Magazine]
English, Scientific journal, A growing body of evidence suggests that immune factors that regulate osteoclast differentiation and bone resorption might be promising therapeutic agents for the treatment of osteoporosis. The expression of CLCF1, an immune cell-derived molecule, has been reported to be reduced in patients with postmenopausal osteoporosis. This suggests that it may be involved in bone remodeling. Thus, we explored the functional role of CLCF1 in osteoclastogenesis and bone loss associated with osteoporosis. Surprisingly, the administration of recombinant CLCF1 repressed excessive bone loss in ovariectomized mice and prevented RANKL-induced bone loss in calvarial mouse model. Likewise, the addition of recombinant CLCF1 to RANKL-stimulated monocytes resulted in a significant suppression in the number of differentiated osteoclasts with small resorption areas being observed on dentine slices in vitro. At the same dosage, CLCF1 did not exhibit any detectable negative effects on the differentiation of osteoblasts. Mechanistically, the inhibition of osteoclast differentiation by the CLCF1 treatment appears to be related to the activation of interferon signaling (IFN) and the suppression of the NF-κB signaling pathway. Interestingly, the expression of the main components of IFN-signaling namely, STAT1 and IRF1, was detected in macrophages as early as 1 h after stimulation with CLCF1. Consistent with these results, the blockade of STAT1 in macrophages abolished the inhibitory effect of CLCF1 on osteoclast differentiation in vitro. These collective findings point to a novel immunoregulatory function of CLCF1 in bone remodeling and highlight it as a potentially useful therapeutic agent for the treatment of osteoporosis.

Risks vs. benefits of switching therapy in patients with postmenopausal osteoporosis.
Hotaka Ishizu, Kosuke Arita, Mohamad Alaa Terkawi, Tomohiro Shimizu, Norimasa Iwasaki
Expert review of endocrinology & metabolism, 16, 5, 1, 12, 26 Jul. 2021, [International Magazine]
English, Scientific journal, Introduction: Osteoporosis is characterized by the fragility of bones, leading to fractures and, consequently, the deterioration of functional capacity and quality of life. Postmenopausal women, in particular, are prone to osteoporosis and often require anti-osteoporosis treatment. In the last few decades, various anti-osteoporosis drugs have been approved for clinical use. In an aging society, osteoporosis cannot be treated using a single agent; therefore, switching therapy is an important treatment strategy.Areas covered: This review covers switching therapy in patients with postmenopausal osteoporosis. It's extremely important to understand the characteristics of each drug including; limitations on the duration of use, side effects due to long-term use (such as atypical femur fracture and osteonecrosis of the jaw) or discontinuation (such as rebound phenomenon), compliance, and ability to prevent fractures. We review and summarize the risks and benefits of switching therapy.Expert opinion: When switching therapy, the order of drug administration is important. Routine monitoring should be continued after switching treatments. We recommend first using osteoanabolic agents in postmenopausal women with severe osteoporosis. In addition, identifying predictors of the efficacy and side effects of treatment may help prevent the inappropriate use of drugs for the treatment of osteoporosis.

Targeting thymidine phosphorylase as a potential therapy for bone loss associated periprosthetic osteolysis
Gen Matsumae, Tomohiro Shimizu, Yuan Tian, Daisuke Takahashi, Taku Ebata, Hend Alhasan, Shunichi Yokota, Ken Kadoya, Mohamad Alaa Terkawi, Norimasa Iwasaki
Bioengineering & Translational Medicine, 6, 3, e10232, Wiley, 19 May 2021, [Corresponding author], [International Magazine]
English, Scientific journal, Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.

Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis
Taku Ebata, Mohamad Alaa Terkawi, Masanari Hamasaki, Gen Matsumae, Tomohiro Onodera, Mahmoud Khamis Aly, Shunichi Yokota, Hend Alhasan, Tomohiro Shimizu, Daisuke Takahashi, Kentaro Homan, Ken Kadoya, Norimasa Iwasaki
iScience, 24, 6, 102643, 102643, Elsevier BV, May 2021, [Corresponding author], [International Magazine]
English, Scientific journal, Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.

Finite element analysis of double-plate fixation using reversed locking compression-distal femoral plates for Vancouver B1 periprosthetic femoral fractures.
Daisuke Takahashi, Yoshihiro Noyama, Tsuyoshi Asano, Tomohiro Shimizu, Tohru Irie, Mohamad Alaa Terkawi, Norimasa Iwasaki
BMC musculoskeletal disorders, 22, 1, 276, 276, 13 Mar. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Internal fixation is recommended for treating Vancouver B1 periprosthetic femoral fractures. Although several fixation procedures have been developed with high fixation stability and union rates, long-term weight-bearing constructs are still lacking. Therefore, the aim of the present study was to evaluate the stability of a double-plate procedure using reversed contralateral locking compression-distal femoral plates for fixation of Vancouver B1 periprosthetic femoral fractures under full weight-bearing. METHODS: Single- and double-plate fixation procedures for locking compression-distal femoral plates were analysed under an axial load of 1,500 N by finite element analysis and biomechanical loading tests. A vertical loading test was performed to the prosthetic head, and the displacements and strains were calculated based on load-displacement and load-strain curves generated by the static compression tests. RESULTS: The finite element analysis revealed that double-plate fixation significantly reduced stress concentration at the lateral plate place on the fracture site. Under full weight-bearing, the maximum von Mises stress in the lateral plate was 268 MPa. On the other hand, the maximum stress in the single-plating method occurred at the defect level of the femur with a maximum stress value of 1,303 MPa. The principal strains of single- and double-plate fixation were 0.63 % and 0.058 %, respectively. Consistently, in the axial loading test, the strain values at a 1,500 N loading of the single- and double-plate fixation methods were 1,274.60 ± 11.53 and 317.33 ± 8.03 (× 10- 6), respectively. CONCLUSIONS: The present study suggests that dual-plate fixation with reversed locking compression-distal femoral plates may be an excellent treatment procedure for patients with Vancouver B1 fractures, allowing for full weight-bearing in the early postoperative period.

Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model.
Yuan Tian, Tomohiro Onodera, Mohamad Alaa Terkawi, Koji Iwasaki, Ryosuke Hishimura, Dawei Liang, Takuji Miyazaki, Norimasa Iwasaki
International journal of molecular sciences, 22, 5, 04 Mar. 2021, [International Magazine]
English, Scientific journal, Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.

人工関節術後無菌性緩みにおけるチミジンホスホリラーゼの機能と骨吸収メカニズムの解明
松前 元, アラー・テルカウィ, 横田 隼一, 江畑 拓, ヘンド・アルハサン, 清水 智弘, 高橋 大介, 角家 健, 岩崎 倫政
北海道整形災害外科学会雑誌, 63, 139th suppl, 18, 18, 北海道整形災害外科学会, 2021
Japanese

Long-Term Clinical and Radiological Outcomes of Primary Total Hip Arthroplasty with Modular Femoral Stem in Middle-Aged Asian Patients.
Kaname Takahashi, Tomohiro Shimizu, Tsuyoshi Asano, Mohamad Alaa Terkawi, Norimasa Iwasaki, Daisuke Takahashi
The Journal of arthroplasty, 35, 12, 3650, 3655, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: There is insufficient information regarding the outcome of primary total hip arthroplasty (THA) with the modular femoral stem in middle-aged patients. This study aimed to assess long-term clinical and radiological outcomes of primary THA using the original or modified modular hip system (S-ROM) in middle-aged Asian patients. METHODS: A retrospective review identified 98 primary THAs that used a modular stem and were undertaken between 1997 and 2009 in patients younger than 58 years, for whom at least 5 years of follow-up data were available. Clinical data and radiograph assessments were reviewed to analyze differences between the original and modified modular stem groups. RESULTS: The mean patient follow-up duration was 148.3 months, and the follow-up ratio was 89.1%. The Kaplan-Meier analysis revealed that the survival rate of both stems was 98.9% at 10 years and 89.8% at 15 years. Although no statistically significant differences in the survival rate were observed between the stem designs, the original stem group had increased incidence of thigh pain compared with the modified stem group. In total, 12 and 54 hips showed change in stem alignment and osteolysis, respectively. CONCLUSION: The findings of this study show that the modular stems have a high survival rate, and results suggest positive outcomes among the Asian population over the long term. Although there were very few differences between the stem designs, the results suggest that the modified modular stem could prevent thigh pain and that selection of the implant based on the bone shape is important for THA.

摩耗軟骨片による滑膜炎が誘導する軟骨細胞新規分泌因子「Flightless I」の機能解析
江畑 拓, Terkawi Alaa, 小野寺 智洋, 木田 博朗, 松前 元, 田 園, Alhasan Hend, 濱崎 雅成, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1690, S1690, (公社)日本整形外科学会, Sep. 2020
Japanese

XCL1/lymphotactin阻害による病的骨吸収抑制効果の検討
Terkawi Alaa, 田 園, 松前 元, 木田 博朗, 高橋 大介, 江畑 拓, Alhasan Hend, 清水 智弘, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1706, S1706, (公社)日本整形外科学会, Sep. 2020
Japanese

人工関節術後無菌性緩みにおけるチミジンホスホリラーゼの機能と骨吸収メカニズムの解明
松前 元, Terkawi Alaa, 木田 博朗, 江畑 拓, 田 園, Alhasan Hend, 清水 智弘, 高橋 大介, 角家 健, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S1711, S1711, (公社)日本整形外科学会, Sep. 2020
Japanese

ビタミンE添加超高分子量ポリエチレンインプラントにおける人工関節置換術後無菌性緩みを抑制する至適濃度の検討
木田 博朗, Terkawi Alaa, 松前 元, 江畑 拓, 田 園, Alhasan Hend, 清水 智弘, 高橋 大介, 岩崎 倫政
日本整形外科学会雑誌, 94, 8, S2017, S2017, (公社)日本整形外科学会, Sep. 2020
Japanese

Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis.
Masanari Hamasaki, Mohamad Alaa Terkawi, Tomohiro Onodera, Yuan Tian, Taku Ebata, Gen Matsumae, Hend Alhasan, Daisuke Takahashi, Norimasa Iwasaki
Scientific reports, 10, 1, 7558, 7558, 05 May 2020, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages play principal role in development of synovitis. Our earlier study suggests that interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments. To this end, we analyzed the transcriptional profiling of murine macrophages exposed to cartilage fragments by RNA sequencing. A total 153 genes were differentially upregulated, and 105 genes were down-regulated in response to cartilage fragments. Bioinformatic analysis revealed that the most significantly enriched terms of the upregulated genes included scavenger receptor activity, integrin binding activity, TNF signaling, and toll-like receptor signaling. To further confirm our results, immunohistochemical staining was performed to detected regulated molecules in synovial tissues of OA patients. In consistence with RNA-seq results, MARCO, TLR2 and ITGα5 were mainly detected in the intima lining layer of synovial tissues. Moreover, blockade of TLR2 or ITGα5 but not Marco using specific antibody significantly reduced production of TNF-α in stimulated macrophages by cartilage fragments. Our data suggested that blocking TLR2 or ITGα5 might be promising therapeutic strategy for treating progressive osteoarthritis.

Which Contributes to Meniscal Repair, the Synovium or the Meniscus? An In Vivo Rabbit Model Study With the Freeze-Thaw Method.
WooYoung Kim, Tomohiro Onodera, Eiji Kondo, Mohamad Alaa Terkawi, Kentaro Homan, Ryosuke Hishimura, Norimasa Iwasaki
The American journal of sports medicine, 48, 6, 1406, 1415, May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: During meniscal tissue repair, the origin of the reparative cells of damaged meniscal tissue remains unclear. HYPOTHESIS: Comparison of the influence between meniscal and synovial tissues on meniscal repair by the in vivo freeze-thaw method would clarify the origin of meniscal reparative cells. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 mature Japanese white rabbits were divided into 4 groups according to the tissue (meniscal or synovial) that received freeze-thaw treatment. The meniscus of each group had a 2 mm-diameter cylindrical defect filled with alginate gel. Macroscopic and histologic evaluations of the reparative tissues were performed at 1, 3, and 6 weeks postoperatively. Additional postoperative measurements included cell density, which was the number of meniscal cells in the cut area per cut area (mm2) of meniscus; cell density ratio, which was the cell density of the sample from each group per the average cell density of the intact meniscus; and cell death rate, which was the number of cells stained by propidium iodide per the number of cells stained by Hoechst 33342 of the meniscal tissue adjacent to the defect. RESULTS: The macroscopic and histologic evaluations of the non-synovium freeze-thaw groups were significantly superior to those of the synovium freeze-thaw groups at 3 and 6 weeks postoperatively. Additionally, the meniscal cell density ratio and cell death rate in the freeze-thaw groups were significantly lower than those in the non-meniscal freeze-thaw groups at 3 and 6 weeks postoperatively. CONCLUSION: The freeze-thawed meniscus recovered few cells in its tissue even after 6 weeks. However, the defect was filled with fibrochondrocytes and proteoglycan when the synovium was intact. On the basis of these results, it is concluded that synovial cells are the primary contributors to meniscal injury repair. CLINICAL RELEVANCE: In meniscal tissue engineering, there is no consensus on the best cell source for meniscal repair. Based on this study, increasing the synovial activity and contribution should be the main objective of meniscal tissue engineering. This study can establish the foundation for future meniscal tissue engineering.

人工関節置換術後無菌性緩みに対するビタミンE添加ポリエチレンインプラントの至適濃度の検討
木田 博朗, Alaa Terkawi, 松前 元, 江畑 拓, 高橋 大介, 岩崎 倫政
北海道整形災害外科学会雑誌, 62, 138th suppl, 5, 5, 北海道整形災害外科学会, 2020
Japanese

First molecular identification of trypanosoma evansi from cattle in Syria
Megasari Marsela, Kyoko Hayashida, Alaa Terkawi, Xuenan Xuan, Chihiro Sugimoto, Junya Yamagishi
Japanese Journal of Veterinary Research, 68, 2, 117, 127, Hokkaido University, 2020
English, Scientific journal

Blockade of XCL1/Lymphotactin Ameliorates Severity of Periprosthetic Osteolysis Triggered by Polyethylene-Particles.
Yuan Tian, Mohamad Alaa Terkawi, Tomohiro Onodera, Hend Alhasan, Gen Matsumae, Daisuke Takahashi, Masanari Hamasaki, Taku Ebata, Mahmoud Khamis Aly, Hiroaki Kida, Tomohiro Shimizu, Keita Uetsuki, Ken Kadoya, Norimasa Iwasaki
Frontiers in immunology, 11, 1720, 1720, 2020, [Corresponding author], [International Magazine]
English, Scientific journal, Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.

Babesia microti Confers Macrophage-Based Cross-Protective Immunity Against Murine Malaria.
Artemis Efstratiou, Eloiza May S Galon, Guanbo Wang, Kousuke Umeda, Daisuke Kondoh, Mohamad Alaa Terkawi, Aiko Kume, Mingming Liu, Aaron Edmond Ringo, Huanping Guo, Yang Gao, Seung-Hun Lee, Jixu Li, Paul Franck Adjou Moumouni, Yoshifumi Nishikawa, Hiroshi Suzuki, Ikuo Igarashi, Xuenan Xuan
Frontiers in cellular and infection microbiology, 10, 193, 193, 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Malaria and babesiosis, the two primary intraerythrocytic protozoan diseases of humans, have been reported in multiple cases of co-infection in endemic regions. As the geographic range and incidence of arthropod-borne infectious diseases is being affected by climate change, co-infection cases with Plasmodium and Babesia are likely to increase. The two parasites have been used in experimental settings, where prior infection with Babesia microti has been shown to protect against fatal malarial infections in mice and primates. However, the immunological mechanisms behind such phenomena of cross-protection remain unknown. Here, we investigated the effect of a primary B. microti infection on the outcome of a lethal P. chabaudi challenge infection using a murine model. Simultaneous infection with both pathogens led to high mortality rates in immunocompetent BALB/c mice, similar to control mice infected with P. chabaudi alone. On the other hand, mice with various stages of B. microti primary infection were thoroughly immune to a subsequent P. chabaudi challenge. Protected mice exhibited decreased levels of serum antibodies and pro-inflammatory cytokines during early stages of challenge infection. Mice repeatedly immunized with dead B. microti quickly succumbed to P. chabaudi infection, despite induction of high antibody responses. Notably, cross-protection was observed in mice lacking functional B and T lymphocytes. When the role of other innate immune effector cells was examined, NK cell-depleted mice with chronic B. microti infection were also found to be protected against P. chabaudi. Conversely, in vivo macrophage depletion rendered the mice vulnerable to P. chabaudi. The above results show that the mechanism of cross-protection conferred by B. microti against P. chabaudi is innate immunity-based, and suggest that it relies predominantly upon the function of macrophages. Further research is needed for elucidating the malaria-suppressing effects of babesiosis, with a vision toward development of novel tools to control malaria.

人工関節置換術後の無菌性緩みにおけるマクロファージ由来チミジンホスホリラーゼの機能解析　　　　　　　　　　　　　　　
松前 元, Terkawi Alaa, 江畑 拓, 木田 博朗, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 180, 180, 日本バイオマテリアル学会, Nov. 2019
Japanese

人工関節置換術後のポリエチレン摩耗粉による炎症性骨吸収及び破骨細胞発現におけるannexin A1の機能解析　　　　　　　　　　　　　　　
Terkawi Alaa, Alhasan Hend, 松前 元, 江畑 拓, 木田 博朗, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 181, 181, 日本バイオマテリアル学会, Nov. 2019
Japanese

人工関節置換術後無菌性緩みに対するビタミンE添加ポリエチレンインプラントの至適濃度の検討　　　　　　　　　　　　　　　
木田 博朗, Terkawi Alaa, 松前 元, 江畑 拓, 高橋 大介, 岩崎 倫政
日本バイオマテリアル学会大会予稿集, 41回, 182, 182, 日本バイオマテリアル学会, Nov. 2019
Japanese

Cocktail Babesia bovis antigens for global detection of Babesia bovis infection in cattle.
Shimaa El-Sayed, Mohamed Abdo Rizk, MohamadAlaa Terkawi, Ikuo Igarashi
Experimental parasitology, 206, 107758, 107758, Nov. 2019, [International Magazine]
English, Scientific journal, The diagnostic performance of a cocktail formula consisting of two Babesia (B.) bovis recombinant proteins, including spherical body protein 1 (BbSBP-1) and spherical body protein 4 (BbSBP-4), was evaluated in the present study for the global detection of B. bovis infection in cattle and for the differentiation between B. bovis and B. bigemina infections. The efficacy and the practicality of the rBbSBP-1 and rBbSBP-4 cocktail formula for differentiation between the infection caused by both parasites were assessed using indirect enzyme-linked immunosorbent assay (iELISA) with serum samples collected from cattle experimentally infected by B. bovis (n = 33) or B. bigemina (n = 30). Cocktail antigen exhibited the highest optical density (OD) values with B. bovis-infected sera and the lowest OD values with normal bovine sera or B. bigemina-infected sera in comparison with the single antigen. A total of 581 field serum samples collected from four countries with known B. bovis endemicity: Ghana (n = 154), Egypt (n = 162), Thailand (n = 96), and South Africa (n = 169) were screened also in the current study using iELISA and the results were compared to those of indirect fluorescent antibody test (IFAT) as a reference. A cocktail formula (rBbSBP-1 and rBbSBP-4) exhibited the highest concordance rate (89.90%) and kappa value (0.73). The obtained results revealed the reliability of the rBbSBP-1 and rBbSBP-4 cocktail antigen for the detection of specific antibodies to B. bovis in cattle and demonstrated the usefulness of cocktail antigen for differentiation between B. bovis and B. bigemina infections compared with the single antigen in cattle, which will be useful for epidemiological surveys and control of bovine babesiosis.

Minimum Ten-Year Outcomes of Partial Ulnar Nerve Transfer for Restoration of Elbow Flexion in Patients with Upper Brachial Plexus Injury.
Yusuke Nagano, Daisuke Kawamura, Alaa Terkawi, Atsushi Urita, Yuichiro Matsui, Norimasa Iwasaki
The journal of hand surgery Asian-Pacific volume, 24, 3, 283, 288, Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background: Partial ulnar nerve transfer to the biceps motor branch of the musculocutaneous nerve (Oberlin's transfer) is a successful approach to restore elbow flexion in patients with upper brachial plexus injury (BPI). However, there is no report on more than 10 years subjective and objective outcomes. The purpose of this study was to clarify the long-term outcomes of Oberlin's transfer based on the objective evaluation of elbow flexion strength and subjective functional evaluation of patients. Methods: Six patients with BPI who underwent Oberlin's transfer were reviewed retrospectively by their medical records. The mean age at surgery was 29.5 years, and the mean follow-up duration was 13 years. The objective functional outcomes were evaluated by biceps muscle strength using the Medical Research Council (MRC) grade at preoperative, postoperative, and final follow-up. The patient-derived subjective functional outcomes were evaluated using the Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire at final follow-up. Results: All patients had MRC grade 0 (M0) or 1 (M1) elbow flexion strength before operation. Four patients gained M4 postoperatively and maintained or increased muscle strength at the final follow-up. One patient gained M3 postoperatively and at the final follow-up. Although one patient achieved M4 postoperatively, the strength was reduced to M2 due to additional disorder. The mean score of QuickDASH was 36.5 (range, 7-71). Patients were divided into two groups; three patients had lower scores and the other three patients had higher scores of QuickDASH. Conclusions: Oberlin's transfer is effective in the restoration of elbow flexion and can maintain the strength for more than 10 years. Patients with upper BPI with restored elbow flexion strength and no complicated nerve disorders have over ten-year subjective satisfaction.

Effects of femoral bone defect morphology on initial polished tapered stem stability in massive defect model: a biomechanical study.
Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Tomohiro Shimizu, Ryuta Arai, Alaa Muhammad Terkawi, Yoichi M Ito, Norimasa Iwasaki
BMC musculoskeletal disorders, 20, 1, 355, 355, 01 Aug. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Good outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads. METHODS: Initial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5 cm × width 2 cm), Short (2.5 cm × 2 cm), Square (3.2 cm × 3.2 cm), Square with mesh (3.2 cm × 3.2 cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20° or to failure. Strain distributions of the femora were measured using a strain gauge. RESULTS: All Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.4 ± 0.3 Nm/deg.) and Square groups (4.3 ± 0.3 Nm/deg.) was significantly smaller than in the Control group (4.8 ± 0.3 Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 ± 100.9) was significantly the largest (Control, 373.2 ± 129.5, p < 0.001; Long, 883.7 ± 153.3, p = 0.027; Short, 434.5 ± 196.8, p < 0.001; Square with mesh, 256.9 ± 100.8, p < 0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region. CONCLUSIONS: Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the lesser trochanter or defects 3 cm or more in width.

Bilateral subchondral insufficiency fractures of the femoral head in a normally active adolescent patient: A case report.
Hotaka Ishizu, Tomohiro Shimizu, Takuma Kaibara, Tsuyoshi Asano, Mohamad Alaa Terkawi, Daisuke Takahashi, Norimasa Iwasaki
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, S0949-2658(19)30148-4, 2, 492, 494, 05 Jun. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Identification of IL-27 as potent regulator of inflammatory osteolysis associated with vitamin E-blended ultra-high molecular weight polyethylene debris of orthopedic implants.
Mohamad Alaa Terkawi, Ken Kadoya, Daisuke Takahashi, Yuan Tian, Masanari Hamasaki, Gen Matsumae, Hend Alhasan, Sameh Elmorsy, Keita Uetsuki, Tomohiro Onodera, Masahiko Takahata, Norimasa Iwasaki
Acta biomaterialia, 89, 242, 251, 15 Apr. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.

Effects of Ultra-Purified Alginate Gel Implantation on Meniscal Defects in Rabbits.
WooYoung Kim, Tomohiro Onodera, Eiji Kondo, Yasuyuki Kawaguchi, Mohamad Alaa Terkawi, Rikiya Baba, Kazutoshi Hontani, Zenta Joutoku, Shinji Matsubara, Kentaro Homan, Ryosuke Hishimura, Norimasa Iwasaki
The American journal of sports medicine, 47, 3, 640, 650, Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Many tissue-engineered methods for meniscal repair have been studied, but their utility remains unclear. HYPOTHESIS: Implantation of low-endotoxin, ultra-purified alginate (UPAL) gel without cells could induce fibrocartilage regeneration on meniscal defects in rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two mature Japanese White rabbits were divided into 2 groups of 21 animals each. In each animal, a cylindrical defect measuring 2 mm in diameter was created with a biopsy punch on the anterior horn of the medial meniscus. In the control group, no treatment was applied on the left medial meniscal defect. In the UPAL gel group, the right medial meniscal defect was injected with the UPAL gel and gelated by a CaCl2 solution. Samples were evaluated at 3, 6, and 12 weeks postoperatively. For biomechanical evaluation, 6 additional samples from intact animals were used for comparison. RESULTS: The macroscopic score was significantly greater in the UPAL gel group than in the control group at 3 weeks (mean ± SE: 5.6 ± 0.82 vs 3.4 ± 0.83, P = .010), 6 weeks (5.9 ± 0.72 vs 2.5 ± 0.75, P = .026), and 12 weeks (5.2 ± 1.21 vs 1.0 ± 0.63, P = .020). The histological score was significantly greater in the UPAL group than in the control group at 3 weeks (2.1 ± 0.31 vs 1.2 ± 0.25, P = .029) and 12 weeks (2.2 ± 0.55 vs 0.3 ± 0.21, P = .016). The mean stiffness of the reparative tissue in the UPAL gel group was significantly greater than that in the control group at 6 weeks (24.325 ± 3.920 N/mm vs 8.723 ± 1.190 N/mm, P = .006) and at 12 weeks (27.804 ± 6.169 N/mm vs not applicable [because of rupture]). CONCLUSION: The UPAL gel enhanced the spontaneous repair of fibrocartilage tissues in a cylindrical meniscal defect in rabbits. CLINICAL RELEVANCE: These results imply that the acellular UPAL gel may improve the repair of traumatic meniscal injuries.

A Novel Cartilage Fragments Stimulation Model Revealed that Macrophage Inflammatory Response Causes an Upregulation of Catabolic Factors of Chondrocytes In Vitro.
Masanari Hamasaki, Mohamad Alaa Terkawi, Tomohiro Onodera, Kentaro Homan, Norimasa Iwasaki
Cartilage, 12, 1947603519828426, 1947603519828426, 1947603519828426, 01 Feb. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal, OBJECTIVE: Osteoarthritis is a progressive joint disease characterized by cartilage degradation and synovial inflammation. Presence of cartilage fragments in the joint due to degradation of cartilage is thought to be associated with local inflammatory response and progressive osteoarthritic process. Understanding the mechanism by which cartilage fragments elicit this destructive process should aid in designing novel therapeutic approaches. Therefore, objective of current study is to establish an in vitro model to examine the cross-talk between chondrocytes and cartilage fragments-stimulated macrophages. DESIGN: Cartilage fragments were prepared from femoral head cartilages of mice and analyzed using a scanning electron microscope and particle size analyzer. Bone marrow-derived macrophages were co-cultured with cartilage fragments and chondrocytes using transwell co-culture system. Macrophage inflammatory mediators in supernatant of cultures were determined by ELISA and gene expression of macrophages and chondrocyte were quantified by qRT-PCR. RESULTS: Shapes of cartilage fragments were irregular with sizes ranged between 0.54 and 55 μm. Macrophages cultured with cartilage fragments released significantly higher concentrations of TNF-α, IL-6, and NO than those of mock and control. Consistently, gene expressions of TNF-α, IL-6, and MMP-9 were significantly increased in stimulated macrophages. The elevation in production of pro-inflammatory molecules in stimulated macrophages cultures were coincident with an increase in gene expression of chondrocyte MMP-13, iNOS, and IL-6. CONCLUSION: We developed an in vitro co-culture model to study the impact of stimulation of macrophage by cartilage fragments on the expression of chondrocyte carbolic factors. Our results revealed that cartilage fragments triggered macrophages inflammatory response that enhanced the production of chondrocyte catabolic factors.

炎症性骨溶解及び骨吸収におけるNOV(Nephroblastoma overexpressed)の機能解析
松前 元, テルカウィ・アラー, 田 園, 濱崎 雅成, ヘンド・アルハサン, 江畑 拓, 高橋 大介, 角家 健, 岩崎 倫政
北海道整形災害外科学会雑誌, 61, 136th suppl, 29, 29, 北海道整形災害外科学会, 2019
Japanese

Identification of il-27 as potent regulator of osteolysis triggered by of orthopaedic implants debris　　　　　　　　　　　　　　　
Daisuke Takahashi, Mohamad Alaa Terkawi, Gen Matsumae, Yuan Tian, Hend Alhasan, Norimasa Iwasaki.
Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium, 40, 612, Society for Biomaterials, 2019
English, International conference proceedings

Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.
Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Muhammad Alaa Terkawi, Yoichi M Ito, Norimasa Iwasaki
Clinical orthopaedics and related research, 476, 7, 1455, 1465, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. QUESTIONS/PURPOSES: (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? METHODS: We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. RESULTS: In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). CONCLUSIONS: Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. CLINICAL RELEVANCE: Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.

A mathematical model for predicting postoperative leg shortening after curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head.
Tsuyoshi Asano, Daisuke Takahashi, Tomohiro Shimizu, Tohru Irie, Ryuta Arai, Mohamad Alaa Terkawi, Norimasa Iwasaki
PloS one, 13, 12, e0208818, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Despite good clinical outcomes associated with curved intertrochanteric varus osteotomy for the treatment of osteonecrosis of the femoral head, post-operative leg-length discrepancy is frequently reported and might reduce patient satisfaction. Although previous report showed that varus angulation affected post-operative leg-length discrepancy, sufficient varus angulation is the most important factor for obtaining a lateral intact portion. Therefore, to ensure better postoperative outcomes, detection of other parameters associated with leg shortening may prove useful. This study aimed to detect other factors influencing post-operative leg-length discrepancy and to develop a theory for pre-operative planning. The study included 42 hips of 36 patients with osteonecrosis of the femoral head [25 men and 11 women; mean age at the time of surgery, 33.8 years (range, 17 to 53 years)]. Patients were assessed their clinical and radiological results bofore and after surgery. Additionally, a mathematical model was developed to predict leg shortening after curved intertrochanteric varus osteotomy based on the degree of varus angulation and the distance between the femoral head and osteotomy arc centers. Predicted and actual leg shortening in patients were compared to verify the accuracy of our model. Post-operatively, mean varus angle was 21.7° (range, 15 to 38°) and mean leg shortening was 1.7 mm (range, -5.1 to 11.4 mm). Univariate analysis showed that varus angulation and lateral shift of the osteotomy arc might influence the degree of leg shortening. Furthermore, mathematically predicted leg shortening significantly correlated with actual leg shortening (r = 0.905, p < 0.001), suggesting the usefulness of our model for predicting complications of curved intertrochanteric varus osteotomy. This study indicates the importance of not positioning the center of the osteotomy arc lateral from the center of the femoral head to minimize leg shortening after curved intertrochanteric osteotomy.

Differential Gene Expression Profile of Human Neutrophils Cultured with Plasmodium falciparum-Parasitized Erythrocytes.
Mohamad Alaa Terkawi, Ryo Takano, Kentaro Kato
Journal of immunology research, 2018, ID 6709424, 6709424, 6709424, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Neutrophils (PMNs) are the most abundant cellular component of our innate immune system, where they play central roles in the pathogenesis of and resistance to a broad range of diseases. However, their roles in malarial infection remain poorly understood. Therefore, we examined the transcriptional gene profile of human PMNs in response to Plasmodium falciparum-parasitized erythrocytes (iRBCs) by using oligonucleotide microarrays. Results revealed that PMNs induced a broad and vigorous set of changes in gene expression in response to malarial parasites, represented by 118 upregulated and 216 downregulated genes. The transcriptional response was characterized by the upregulation of numerous genes encoding multiple surface receptors, proteins involved in signal transduction pathways, and defense response proteins. This response included a number of genes which are known to be involved in the pathogenesis of malaria and other inflammatory diseases. Gene enrichment analysis suggested that the biological pathways involved in the PMN responses to the iRBCs included insulin receptor, Jak-STAT signaling pathway, mitogen-activated protein kinase (MAPK), and interleukin and interferon-gamma (IFN-γ) signaling pathways. The current study provides fundamental knowledge on the molecular responses of neutrophils to malarial parasites, which may aid in the discovery of novel therapeutic interventions.

Transcriptional profile of human macrophages stimulated by ultra-high molecular weight polyethylene particulate debris of orthopedic implants uncovers a common gene expression signature of rheumatoid arthritis.
Mohamad Alaa Terkawi, Masanari Hamasaki, Daisuke Takahashi, Masahiro Ota, Ken Kadoya, Tomoyo Yutani, Keita Uetsuki, Tsuyoshi Asano, Tohru Irie, Ryuta Arai, Tomohiro Onodera, Masahiko Takahata, Norimasa Iwasaki
Acta biomaterialia, 65, 417, 425, Acta Materialia Inc, Jan. 2018, [Peer-reviewed], [Corresponding author], [International Magazine]
English, Scientific journal

Molecular identification and antigenic characterization of Babesia divergens Erythrocyte Binding Protein (BdEBP) as a potential vaccine candidate.
Shimaa Abd El-Salam El-Sayed, Mohamed Abdo Rizk, Mohamad Alaa Terkawi, Naoaki Yokoyama, Ikuo Igarashi
Parasitology international, 66, 6, 721, 726, Dec. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Chemotherapeutic efficacies of a clofazimine and diminazene aceturate combination against piroplasm parasites and their AT-rich DNA-binding activity on Babesia bovis.
Bumduuren Tuvshintulga, Mahmoud AbouLaila, Thillaiampalam Sivakumar, Dickson Stuart Tayebwa, Sambuu Gantuya, Khandsuren Naranbaatar, Aki Ishiyama, Masato Iwatsuki, Kazuhiko Otoguro, Satoshi Ōmura, Mohamad Alaa Terkawi, Azirwan Guswanto, Mohamed Abdo Rizk, Naoaki Yokoyama, Ikuo Igarashi
Scientific reports, 7, 1, 13888, 13888, 24 Oct. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Evaluation of immunochromatographic test (ICT) strips for the serological detection of Babesia bovis and Babesia bigemina infection in cattle from Western Java, Indonesia.
Azirwan Guswanto, Puttik Allamanda, Euis Siti Mariamah, Tserendorf Munkjargal, Bumduuren Tuvshintulga, Hitoshi Takemae, Thillaiampalam Sivakumar, Mahmoud AbouLaila, Mohamad Alaa Terkawi, Madoka Ichikawa-Seki, Yoshifumi Nishikawa, Naoaki Yokoyama, Ikuo Igarashi
Veterinary parasitology, 239, 76, 79, 30 May 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

A rare case of multiple phosphaturic mesenchymal tumors along a tendon sheath inducing osteomalacia.
Ryuta Arai, Tomohiro Onodera, Mohamad Alaa Terkawi, Tomoko Mitsuhashi, Eiji Kondo, Norimasa Iwasaki
BMC musculoskeletal disorders, 18, 1, 79, 79, 13 Feb. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum.
Mohamad Alaa Terkawi, Ryo Takano, Atsushi Furukawa, Fumi Murakoshi, Kentaro Kato
Scientific reports, 7, 41772, 41772, 41772, 09 Feb. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate.
Ryuta Arai, Daisuke Takahashi, Masahiro Inoue, Tohru Irie, Tsuyoshi Asano, Takuya Konno, Mohamad Alaa Terkawi, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
BMC musculoskeletal disorders, 18, 1, 24, 24, 19 Jan. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Correction: Human babesiosis: Indication of a molecular mimicry between thrombospondin domains from a novel Babesia microti BmP53 protein and host platelets molecules.
Ahmed Abdelmoniem Mousa, Daniel Barry Roche, Mohamad Alaa Terkawi, Kyohko Kameyama, Ketsarin Kamyingkird, Patrick Vudriko, Akram Salama, Shinuo Cao, Sahar Orabi, Hanem Khalifa, Mohamed Ahmed, Mabrouk Attia, Ahmed Elkirdasy, Yoshifumi Nishikawa, Xuenan Xuan, Emmanuel Cornillot
PloS one, 12, 12, e0189383, 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal, [This corrects the article DOI: 10.1371/journal.pone.0185372.].

Human babesiosis: Indication of a molecular mimicry between thrombospondin domains from a novel Babesia microti BmP53 protein and host platelets molecules.
Ahmed Abdelmoniem Mousa, Daniel Barry Roche, Mohamad Alaa Terkawi, Kyohko Kameyama, Ketsarin Kamyingkird, Patrick Vudriko, Akram Salama, Shinuo Cao, Sahar Orabi, Hanem Khalifa, Mohamed Ahmed, Mabrouk Attia, Ahmed Elkirdasy, Yoshifumi Nishikawa, Xuenan Xuan, Emmanuel Cornillot
PloS one, 12, 10, e0185372, 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Immunization with Toxoplasma gondii peroxiredoxin 1 induces protective immunity against toxoplasmosis in mice.
Ragab M Fereig, Yasuhiro Kuroda, Mohamad Alaa Terkawi, Motamed Elsayed Mahmoud, Yoshifumi Nishikawa
PloS one, 12, 4, e0176324, 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Isolation and co-cultivation of human macrophages and neutrophils with Plasmodium falciparum-parasitized erythrocytes: An optimized system to study the phagocytic activity to malarial parasites.
Mohamad Alaa Terkawi, Ryo Takano, Kentaro Kato
Parasitology international, 65, 5 Pt B, 545, 548, Oct. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular detection of spotted fever group rickettsiae in Amblyomma variegatum ticks from Benin.
Paul Franck Adjou Moumouni, Mohamad Alaa Terkawi, Charoonluk Jirapattharasate, Shinuo Cao, Mingming Liu, Ryo Nakao, Rika Umemiya-Shirafuji, Naoaki Yokoyama, Chihiro Sugimoto, Kozo Fujisaki, Hiroshi Suzuki, Xuenan Xuan
Ticks and tick-borne diseases, 7, 5, 828, 833, Elsevier GmbH, Jul. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular identification and antigenic characterization of a merozoite surface antigen and a secreted antigen of Babesia canis (BcMSA1 and BcSA1).
Mo Zhou, Shinuo Cao, Yuzi Luo, Mingming Liu, Guanbo Wang, Paul Franck Adjou Moumouni, Charoonluk Jirapattharasate, Aiko Iguchi, Patrick Vudriko, Mohamad Alaa Terkawi, Mario Löwenstein, Angela Kern, Yoshifumi Nishikawa, Hiroshi Suzuki, Ikuo Igarashi, Xuenan Xuan
Parasites & vectors, 9, 1, 257, 257, BioMed Central Ltd., 03 May 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Dextran sulfate inhibits acute Toxoplama gondii infection in pigs.
Kentaro Kato, Yuho Murata, Noriyuki Horiuchi, Atsuko Inomata, Mohamad Alaa Terkawi, Akiko Ishiwa, Yohsuke Ogawa, Shinya Fukumoto, Fumikazu Matsuhisa, Kenji Koyama
Parasites & vectors, 9, 134, 134, 09 Mar. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.
Mohamad Alaa Terkawi, Maki Nishimura, Hidefumi Furuoka, Yoshifumi Nishikawa
Infection and immunity, 84, 3, 845, 55, 11 Jan. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Characterization of Toxoplasma gondii glyoxalase 1 and evaluation of inhibitory effects of curcumin on the enzyme and parasite cultures.
Youn-Kyoung Goo, Junya Yamagishi, Akio Ueno, Mohamad Alaa Terkawi, Gabriel Oluga Aboge, Dongmi Kwak, Yeonchul Hong, Dong-Il Chung, Makoto Igarashi, Yoshifumi Nishikawa, Xuenan Xuan
Parasites & vectors, 8, 1, 654, 654, BioMed Central Ltd., 23 Dec. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cocktail of Theileria equi antigens for detecting infection in equines
Shimaa Abd El-Salam El-Sayed, Mohamed Abdo Rizk, Mohamed Alaa Terkawi, Ahmed Mousa, El Said El Shirbini El Said, Gehad Elsayed, Mohamed Fouda, Naoaki Yokoyama, Ikuo Igarashi
Asian Pacific Journal of Tropical Biomedicine, 5, 12, 977, 981, Hainan Medical University, 01 Dec. 2015, [Peer-reviewed]
English, Scientific journal

Molecular Characterization of Babesia bovis M17 Leucine Aminopeptidase and Inhibition of Babesia Growth by Bestatin.
Gabriel Oluga Aboge, Shinuo Cao, Mohamad Alaa Terkawi, Tatsunori Masatani, Younkyoung Goo, Mahmoud AbouLaila, Yoshifumi Nishikawa, Ikuo Igarashi, Hiroshi Suzuki, Xuenan Xuan
The Journal of parasitology, 101, 5, 536, 41, American Society of Parasitologists, Oct. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular detection and characterization of Babesia bovis, Babesia bigemina, Theileria species and Anaplasma marginale isolated from cattle in Kenya.
Paul Franck Adjou Moumouni, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Tatsunori Masatani, Shinuo Cao, Ketsarin Kamyingkird, Charoonluk Jirapattharasate, Mo Zhou, Guanbo Wang, Mingming Liu, Aiko Iguchi, Patrick Vudriko, Adrian Patalinghug Ybanez, Hisashi Inokuma, Rika Shirafuji-Umemiya, Hiroshi Suzuki, Xuenan Xuan
Parasites & vectors, 8, 1, 496, 496, BioMed Central Ltd., 30 Sep. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites.
Mohamed Abdo Rizk, Shimaa Abd El-Salam El-Sayed, Mohamed Alaa Terkawi, Mohamed Ahmed Youssef, El Said El Shirbini El Said, Gehad Elsayed, Sabry El-Khodery, Maged El-Ashker, Ahmed Elsify, Mosaab Omar, Akram Salama, Naoaki Yokoyama, Ikuo Igarashi
PloS one, 10, 4, e0125276, Public Library of Science, 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.
Mohamad Alaa Terkawi, Shinuo Cao, Maria S Herbas, Maki Nishimura, Yan Li, Paul Franck Adjou Moumouni, Asadullah Hamid Pyarokhil, Daisuke Kondoh, Nobuo Kitamura, Yoshifumi Nishikawa, Kentaro Kato, Naoaki Yokoyama, Jinlin Zhou, Hiroshi Suzuki, Ikuo Igarashi, Xuenan Xuan
Infection and immunity, 83, 1, 8, 16, Jan. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cloning and characterization of aspartic protease 3 of Toxoplasma gondii.
Kamyingkird K, Goo YK, Cao S, Adjou Moumouni PF, Aboge GO, Yamagishi J, Terkawi MA, Masatani T, Yu L, Nishikawa Y, Xuan X
Journal of Protozoology Research, 24, 1, 18, 25, National Research Center for Protozoan Diseases, Dec. 2014
English, Scientific journal

Seroprevalence of Babesia caballi and Theileria equi in horses and mules from Northern Thailand
Kamyingkird K, Yangtara S, Desquesnes M, Cao S, Adjou Moumouni PF, Jittapalapong S, Nimsupan B, Terkawi MA, Masatani T, Nishikawa Y, Igarashi I, Xuan X
Journal of Protozoology Research, 24, 1, 11, 17, National Research Center for Protozoan Diseases, Dec. 2014
English, Scientific journal

Plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice.
Mohamad Alaa Terkawi, Yasuhiro Kuroda, Shinya Fukumoto, Sachi Tanaka, Naoya Kojima, Yoshifumi Nishikawa
Malaria journal, 13, 426, 426, 05 Nov. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular and seroepidemiological survey of Babesia bovis and Babesia bigemina infections in cattle and water buffaloes in the central region of Vietnam.
Yan Li, Yuzi Luo, Shinuo Cao, Mohamad Alaa Terkawi, Dinh Thi Bich Lan, Phung Thang Long, Longzheng Yu, Mo Zhou, Haiyan Gong, Houshuang Zhang, Jinlin Zhou, Naoaki Yokoyama, Hiroshi Suzuki, Xuenan Xuan
Tropical biomedicine, 31, 3, 406, 13, Malaysian Society for Parasitology, Sep. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Mycophenolic acid, mycophenolate mofetil, mizoribine, ribavirin, and 7-nitroindole inhibit propagation of Babesia parasites by targeting inosine 5'-monophosphate dehydrogenase.
Shinuo Cao, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Mo Zhou, Ketsarin Kamyingkird, Paul Franck Adjou Moumouni, Tatsunori Masatani, Ikuo Igarashi, Yoshifumi Nishikawa, Hiroshi Suzuki, Xuenan Xuan
The Journal of parasitology, 100, 4, 522, 6, American Society of Parasitologists, Aug. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Babesia bovis dihydroorotate dehydrogenase (BboDHODH) is a novel molecular target of drug for bovine babesiosis.
Ketsarin Kamyingkird, Shinuo Cao, Tatsunori Masatani, Paul Franck Adjou Moumouni, Patrick Vudriko, Ahmed Abd El Moniem Mousa, Mohamad Alaa Terkawi, Yoshifumi Nishikawa, Ikuo Igarashi, Xuenan Xuan
The Journal of veterinary medical science, 76, 3, 323, 30, Japanese Society of Veterinary Science, Mar. 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Inhibitory effect of allicin on the growth of Babesia and Theileria equi parasites.
Akram Ahmed Salama, Mahmoud AbouLaila, Mohamad Alaa Terkawi, Ahmed Mousa, Ahmed El-Sify, Mahmoud Allaam, Ahmed Zaghawa, Naoaki Yokoyama, Ikuo Igarashi
Parasitology research, 113, 1, 275, 83, Jan. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cloning and characterization of a 2-Cys peroxiredoxin from Babesia gibsoni
Tatsunori Masatani, Masahito Asada, Madoka Ichikawa-Seki, Miho Usui, Mohamad A. Terkawi, Kei Hayashi, Shin-Ichiro Kawazu, Xuenan Xuan
Journal of Veterinary Medical Science, 76, 1, 139, 143, Jan. 2014, [Peer-reviewed]
English

Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target.
Patrick Vudriko, Tatsunori Masatani, Shinuo Cao, Mohamad Alla Terkawi, Ketsarin Kamyingkird, Ahmed A Mousa, Paul F Adjou Moumouni, Yoshifumi Nishikawa, Xuenan Xuan
Drug target insights, 8, 8, 31, 8, Libertas Academica Ltd., 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Prime-boost vaccination with plasmid DNA followed by recombinant vaccinia virus expressing BgGARP induced a partial protective immunity to inhibit Babesia gibsoni proliferation in dogs.
Shinuo Cao, Ahmed Abdelmoniem Mousa, Gabriel Oluga Aboge, Ketsarin Kamyingkird, Mo Zhou, Paul Franck Adjou Moumouni, Mohamad Alaa Terkawi, Tatsunori Masatani, Yoshifumi Nishikawa, Hiroshi Suzuki, Shinya Fukumoto, Xuenan Xuan
Acta parasitologica, 58, 4, 619, 23, Dec. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular and serological prevalence of Babesia bigemina and Babesia bovis in cattle and water buffalos under small-scale dairy farming in Beheira and Faiyum Provinces, Egypt.
Hany M Ibrahim, Paul F Adjou Moumouni, Khaled Mohammed-Geba, Sherin K Sheir, Ihab S Y Hashem, Shinuo Cao, Mohamad A Terkawi, Ketsarin Kamyingkird, Yoshifumi Nishikawa, Hiroshi Suzuki, Xuenan Xuan
Veterinary parasitology, 198, 1-2, 187, 92, 15 Nov. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Specific antibody to a conserved region of Babesia apical membrane antigen-1 inhibited the invasion of B. bovis into the erythrocyte.
Akram Ahmed Salama, Mohamad Alaa Terkawi, Satoru Kawai, Mahmoud Aboulaila, Mohamed Nayel, Ahmed Mousa, Ahmed Zaghawa, Naoaki Yokoyama, Ikuo Igarashi
Experimental parasitology, 135, 3, 623, 8, Nov. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Identification of a highly antigenic region of subtilisin-like serine protease 1 for serodiagnosis of Neospora caninum infection.
Rochelle Haidee D Ybañez, Mohamad Alaa Terkawi, Kyohko Kameyama, Xuenan Xuan, Yoshifumi Nishikawa
Clinical and vaccine immunology : CVI, 20, 10, 1617, 22, Oct. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular characterization and antigenic properties of a novel Babesia gibsoni glutamic acid-rich protein (BgGARP).
Ahmed Abdelmoniem Mousa, Shinuo Cao, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Ahmed El Kirdasy, Akram Salama, Mabrouk Attia, Mahmoud Aboulaila, Mo Zhou, Ketsarin Kamyingkird, Paul Franck Adjou Moumouni, Tatsunori Masatani, Sami Ahmed Abd El Aziz, Waheed Mohammed Moussa, Bayin Chahan, Shinya Fukumoto, Yoshifumi Nishikawa, Salah Sayed El Ballal, Xuenan Xuan
Experimental parasitology, 135, 2, 414, 20, Oct. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Actin polymerization mediated by Babesia gibsoni aldolase is required for parasite invasion.
Youn-Kyoung Goo, Akio Ueno, Mohamad Alaa Terkawi, G Oluga Aboge, Yamagishi Junya, Makoto Igarashi, Jung-Yeon Kim, Yeon-Chul Hong, Dong-Il Chung, Yoshifumi Nishikawa, Xuenan Xuan
Experimental parasitology, 135, 1, 42, 9, Sep. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

TgGRA23, a novel Toxoplasma gondii dense granule protein associated with the parasitophorous vacuole membrane and intravacuolar network.
Tatsunori Masatani, Tomohide Matsuo, Tetsuya Tanaka, Mohamad Alaa Terkawi, Eung-Goo Lee, Youn-Kyoung Goo, Gabriel Oluga Aboge, Junya Yamagishi, Kei Hayashi, Kyohko Kameyama, Shinuo Cao, Yoshifumi Nishikawa, Xuenan Xuan
Parasitology international, 62, 4, 372, 9, Aug. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Identification, cloning and characterization of BmP41, a common antigenic protein of Babesia microti.
Tatsunori Masatani, Hideo Ooka, Mohamad A Terkawi, Shinuo Cao, Yuzi Luo, Masahito Asada, Kei Hayashi, Yoshifumi Nishikawa, Xuenan Xuan
The Journal of veterinary medical science, 75, 7, 967, 70, 31 Jul. 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Epidemiological survey of Babesia bovis and Babesia bigemina infections of cattle in Philippines.
Longzheng Yu, Mohmad Alaa Terkawi, Mary Jane Cruz-Flores, Florencia G Claveria, Gabriel Oluga Aboge, Junya Yamagishi, Youn-Kyoung Goo, Shinuo Cao, Tatsunori Masatani, Yoshifumi Nishikawa, Xuenan Xuan
The Journal of veterinary medical science, 75, 7, 995, 8, 31 Jul. 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prevalence and genetic diversity of equine piroplasms in Tov province, Mongolia.
Tserendorj Munkhjargal, Thillaiampalam Sivakumar, Badgar Battsetseg, Tserendorj Nyamjargal, Mahmoud Aboulaila, Byambaa Purevtseren, Dorj Bayarsaikhan, Badarch Byambaa, Mohamad Alaa Terkawi, Naoaki Yokoyama, Ikuo Igarashi
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 16, 178, 85, Jun. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Development of an immunochromatographic assay based on dense granule protein 7 for serological detection of Toxoplasma gondii infection.
Mohamad Alaa Terkawi, Kyohko Kameyama, Nazim Hamza Rasul, Xuean Xuan, Yoshifumi Nishikawa
Clinical and vaccine immunology : CVI, 20, 4, 596, 601, Apr. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Farsenyl pyrophosphate synthase is a potential molecular drug target of risedronate in Babesia bovis.
Akio Ueno, Mohamad Alaa Terkawi, Miki Yokoyama, Shinuo Cao, Gabriel Aboge, Mahmoud Aboulaila, Yoshifumi Nishikawa, Xuenan Xuan, Naoaki Yokoyama, Ikuo Igarashi
Parasitology international, 62, 2, 189, 92, 2, Apr. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cloning, characterization and validation of inosine 5'-monophosphate dehydrogenase of Babesia gibsoni as molecular drug target.
Shinuo Cao, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Mo Zhou, Yuzi Luo, Longzheng Yu, Yan Li, Younkyoung Goo, Ketsarin Kamyingkird, Tatsunori Masatani, Hiroshi Suzuki, Ikuo Igarashi, Yoshifumi Nishikawa, Xuenan Xuan
Parasitology international, 62, 2, 87, 94, Apr. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Identification and characterization of an interspersed repeat antigen of Babesia microti (BmIRA).
Shinuo Cao, Yuzi Luo, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Tatsunori Masatani, Hiroshi Suzuki, Ikuo Igarashi, Yoshifumi Nishikawa, Xuenan Xuan
Experimental parasitology, 133, 3, 346, 52, Mar. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Evaluation of in vitro and in vivo inhibitory effects of fusidic acid on Babesia and Theileria parasites.
Akram Ahmed Salama, Mahmoud Aboulaila, Ahmed A Moussa, Mohamed A Nayel, Ahmed El-Sify, Mohamad A Terkawi, Hany Y Hassan, Naoaki Yokoyama, Ikuo Igarashi
Veterinary parasitology, 191, 1-2, 1, 10, 1-2, 16 Jan. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular characterization of a new Babesia bovis thrombospondin-related anonymous protein (BbTRAP2).
Mohamad Alaa Terkawi, Jadsada Ratthanophart, Akram Salama, Mahmoud AbouLaila, Masahito Asada, Akio Ueno, Hend Alhasan, Azirwan Guswanto, Tatsunori Masatani, Naoaki Yokoyama, Yoshifumi Nishikawa, Xuenan Xuan, Ikuo Igarashi
PloS one, 8, 12, e83305, 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular detection of Theileria species in sheep from northern China.
Shinuo Cao, Shoufa Zhang, Lijun Jia, Shujiang Xue, Longzheng Yu, Ketsarin Kamyingkird, Paul Franck Adjou Moumouni, Ahmed Abd El Moniem Moussa, Mo Zhou, Yuanming Zhang, Mohamad Alaa Terkawi, Tatsunori Masatani, Yoshifumi Nishikawa, Xuenan Xuan
The Journal of veterinary medical science, 75, 9, 1227, 30, 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Expression and immunological characterization of the heat shock protein-70 homologue from Babesia bigemina.
Mahmoud AbouLaila, Mohamad Alaa Terkawi, Faasoa Junior Seuseu, Naomi Ota, Alan Caine Costa de Macedo, Naoaki Yokoyama, Xuenan Xuan, Ikuo Igarashi
Veterinary parasitology, 190, 3-4, 401, 10, 3-4, 21 Dec. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Development of a rapid immunochromatographic test using a recombinant thrombospondin-related adhesive protein of Babesia gibsoni.
Youn-Kyoung Goo, Naeun Lee, Mohamad Alaa Terkawi, Yuzi Luo, Gabriel Oluga Aboge, Yoshifumi Nishikawa, Hiroshi Suzuki, Suk Kim, Xuenan Xuan
Veterinary parasitology, 190, 3-4, 595, 8, 21 Dec. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular and immunological characterization of a novel 32-kDa secreted protein of Babesia microti.
Hideo Ooka, Mohamad A Terkawi, Shinuo Cao, Gabriel Aboge, Youn-Kyoung Goo, Yuzi Luo, Yan Li, Yoshifumi Nishikawa, Ikuo Igarashi, Xuenan Xuan
The Journal of parasitology, 98, 5, 1045, 8, 5, Oct. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Inhibitory effects of pepstatin A and mefloquine on the growth of Babesia parasites.
Tserendorj Munkhjargal, Mahmoud AbouLaila, Mohamad Alaa Terkawi, Thillaiampalam Sivakumar, Madoka Ichikawa, Batdorj Davaasuren, Tserendorj Nyamjargal, Naoaki Yokoyama, Ikuo Igarashi
The American journal of tropical medicine and hygiene, 87, 4, 681, 8, 4, Oct. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

C-Terminal region of 48-kDa rhoptry protein for serological detection of Babesia caballi antibodies in horses.
Mohamad Alaa Terkawi, Hend Alhasan, Akio Ueno, Jadsada Ratthanophart, Yuzi Luo, Shinuo Cao, Ketsarin Kamyingkird, Mahmoud Aboulaila, Goo Youn-Kyoung, Yoshifumi Nishikawa, Naoaki Yokoyama, Xuenan Xuan, Ikuo Igarashi
Parasitology international, 61, 3, 493, 6, 3, Sep. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular detection and identification of Babesia bovis and Babesia bigemina in cattle in northern Thailand.
Shinuo Cao, Gabriel Oluga Aboge, Mohamad Alaa Terkawi, Longzheng Yu, Ketsarin Kamyingkird, Yuzi Luo, Yan Li, Youn-Kyoung Goo, Junya Yamagishi, Yoshifumi Nishikawa, Naoaki Yokoyama, Hiroshi Suzuki, Ikuo Igarashi, Ryuichiro Maeda, Tawin Inpankaew, Sathaporn Jittapalapong, Xuenan Xuan
Parasitology research, 111, 3, 1259, 66, Sep. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular and serological prevalence of Babesia bovis and Babesia bigemina in cattle from central region of Syria.
Mohamad Alaa Terkawi, Hend Alhasan, Nguyen Xuan Huyen, Amin Sabagh, Karam Awier, Shinuo Cao, Youn-Kyoung Goo, Gabriel Aboge, Naoaki Yokoyama, Yoshifumi Nishikawa, Abdul Karim Kalb-Allouz, Darem Tabbaa, Ikuo Igarashi, Xuenan Xuan
Veterinary parasitology, 187, 1-2, 307, 11, 1-2, 08 Jun. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Four promising antigens, BgP32, BgP45, BgP47, and BgP50, for serodiagnosis of Babesia gibsoni infection were classified as B. gibsoni merozoite surface protein family.
Youn-Kyoung Goo, Gabriel Oluga Aboge, M Alaa Terkawi, Honglin Jia, Junya Yamagishi, Fujiko Sunaga, Kazuhiko Namikawa, Se-Yeoun Cha, Hyung-Kwan Jang, Suk Kim, Yoshifumi Nishikawa, Xuenan Xuan
Parasitology international, 61, 2, 364, 8, Jun. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

A double antibody sandwich enzyme-linked immunosorbent assay for detection of secreted antigen 1 of Babesia microti using hamster model.
Yuzi Luo, Mohamad Alaa Terkawi, Honglin Jia, Gabriel Oluga Aboge, Youn-Kyoung Goo, Shinuo Cao, Yan Li, Longzheng Yu, Hideo Ooka, Ketsarin Kamyingkird, Tatsunori Masatani, Shoufa Zhang, Yoshifumi Nishikawa, Ikuo Igarashi, Xuenan Xuan
Experimental parasitology, 130, 2, 178, 82, Feb. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Macrophages are critical for cross-protective immunity conferred by Babesia microti against Babesia rodhaini infection in mice.
Yan Li, Mohamad Alaa Terkawi, Yoshifumi Nishikawa, Gabriel Oluga Aboge, Yuzi Luo, Hideo Ooka, Youn-Kyoung Goo, Longzheng Yu, Shinuo Cao, Yongfeng Sun, Junya Yamagishi, Tatsunori Masatani, Naoaki Yokoyama, Ikuo Igarashi, Xuenan Xuan
Infection and immunity, 80, 1, 311, 20, Jan. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Serological survey of Babesia bovis and Babesia bigemina in cattle in South Africa.
Mohamad Alaa Terkawi, Oriel M M Thekisoe, Charles Katsande, Abdalla A Latif, Ben J Mans, Olivier Matthee, Nozipho Mkize, Nomsa Mabogoane, Frances Marais, Naoaki Yokoyama, Xuenan Xuan, Ikuo Igarashi
Veterinary parasitology, 182, 2-4, 337, 42, 2-4, 15 Dec. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular prevalence of different genotypes of Theileria orientalis detected from cattle and water buffaloes in Thailand.
Khukhuu Altangerel, Thillaiampalam Sivakumar, Tawin Inpankaew, Sathaporn Jittapalapong, Mohamad Alaa Terkawi, Akio Ueno, Xuenan Xuan, Ikuo Igarashi, Naoaki Yokoyama
The Journal of parasitology, 97, 6, 1075, 9, 6, Dec. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Expression of truncated Babesia gibsoni thrombospondin-related adhesive proteins in Escherichia coli and evaluation of their diagnostic potential by enzyme-linked immunosorbent assay.
S Narantsatsral, Youn-Kyoung Goo, B Battsetseg, P Myagmarsuren, Mohamad Alaa Terkawi, Takehisa Soma, Yuzi Luo, Yan Li, Shinuo Cao, Longzheng Yu, Ketsarin Kamyingkird, Gabriel Oluga Aboge, Yoshifumi Nishikawa, Xuenan Xuan
Experimental parasitology, 129, 2, 196, 202, Oct. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Secretion of a new spherical body protein of Babesia bovis into the cytoplasm of infected erythrocytes
Mohamad Alaa Terkawi, Faasoa Junior Seuseu, Putut Eko-Wibowo, Nguyen Xuan Huyen, Yuka Minoda, Mahmoud Aboulaila, Satoru Kawai, Naoaki Yokoyama, Xuenan Xuan, Ikuo Igarashi
Molecular and Biochemical Parasitology, 178, 1-2, 40, 45, 1-2, Jul. 2011, [Peer-reviewed]
English, Scientific journal

Molecular and serological prevalence of Babesia bovis and Babesia bigemina in water buffaloes in the northeast region of Thailand.
Mohamad Alaa Terkawi, Nguyen Xuan Huyen, Cao Shinuo, Tawin Inpankaew, Khuanwalai Maklon, Mahmoud Aboulaila, Akio Ueno, Youn-Kyoung Goo, Naoaki Yokoyama, Sathaporn Jittapalapong, Xuenan Xuan, Ikuo Igarashi
Veterinary parasitology, 178, 3-4, 201, 7, 3-4, 10 Jun. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Identification and characterization of a novel secreted antigen 1 of Babesia microti and evaluation of its potential use in enzyme-linked immunosorbent assay and immunochromatographic test.
Yuzi Luo, Honglin Jia, M Alaa Terkawi, Youn-Kyoung Goo, Suguru Kawano, Hideo Ooka, Yan Li, Longzheng Yu, Shinuo Cao, Junya Yamagishi, Kozo Fujisaki, Yoshifumi Nishikawa, Atsuko Saito-Ito, Ikuo Igarashi, Xuenan Xuan
Parasitology international, 60, 2, 119, 25, 2, Jun. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Immunogenicity of orally administrated recombinant Lactobacillus casei Zhang expressing Cryptosporidium parvum surface adhesion protein P23 in mice.
Geriletu, Rihua Xu, Honglin Jia, Mohamad Alaa Terkawi, Xuenan Xuan, Heping Zhang
Current microbiology, 62, 5, 1573, 80, May 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Drug Discovery against Babesia and Toxoplasma
Mohamad Alaa Terkawi, Ikuo Igarashi
Apicomplexan Parasites: Molecular Approaches toward Targeted Drug Development, 453, 467, Wiley-VCH, 21 Feb. 2011, [Peer-reviewed]
English, In book

Spherical body protein 4 is a new serological antigen for global detection of Babesia bovis infection in cattle.
Mohamad Alaa Terkawi, Nguyen Xuan Huyen, Putut Eko Wibowo, Faasoa Junior Seuseu, Mahmoud Aboulaila, Akio Ueno, Youn-Kyoung Goo, Naoaki Yokoyama, Xuenan Xuan, Ikuo Igarashi
Clinical and vaccine immunology : CVI, 18, 2, 337, 42, 2, Feb. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Babesia microti: molecular and antigenic characterizations of a novel 94-kDa protein (BmP94).
Hideo Ooka, Mohamad Alaa Terkawi, Youn-Kyoung Goo, Yuzi Luo, Yan Li, Junya Yamagishi, Yoshifumi Nishikawa, Ikuo Igarashi, Xuenan Xuan
Experimental parasitology, 127, 1, 287, 93, 1, Jan. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Artesunate, a potential drug for treatment of Babesia infection.
Youn-Kyoung Goo, M Alaa Terkawi, Honglin Jia, G Oluga Aboge, Hideo Ooka, Bryce Nelson, Suk Kim, Fujiko Sunaga, Kazuhiko Namikawa, Ikuo Igarashi, Yoshifumi Nishikawa, Xuenan Xuan
Parasitology international, 59, 3, 481, 6, 3, Sep. 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal

Serodiagnosis of ovine toxoplasmosis in Mongolia by an enzyme-linked immunosorbent assay with recombinant Toxoplasma gondii matrix antigen 1.
Buyannemekh Tumurjav, Mohamad Alaa Terkawi, Houshuang Zhang, Guohong Zhang, Honglin Jia, Youn-Kyoung Goo, Junya Yamagishi, Yoshifumi Nishikawa, Ikuo Igarashi, Chihiro Sugimoto, Xuenan Xuan
The Japanese journal of veterinary research, 58, 2, 111, 9, 2, Aug. 2010, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Babesia gibsoni: identification, expression, localization, and serological characterization of a Babesia gibsoni 22-kDa protein.
Youn-Kyoung Goo, Honglin Jia, Mohamad Alaa Terkawi, Gabriel Oluga Aboge, Junya Yamagishi, Yoshifumi Nishikawa, Suk Kim, Hyung-Kwan Jang, Kozo Fujisaki, Xuenan Xuan
Experimental parasitology, 123, 3, 273, 6, Nov. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular characterizations of three distinct Babesia gibsoni rhoptry-associated protein-1s (RAP-1s).
M A Terkawi, A Amornthep, H Ooka, G Aboge, H Jia, Y-K Goo, B Nelson, J Yamagishi, Y Nishikawa, I Igarashi, S-I Kawazu, K Fujisaki, X Xuan
Parasitology, 136, 10, 1147, 60, 10, Sep. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Detection of Babesia gibsoni by reaction of phage display single chain antibodies with P50 proteins.
Yoshino Hirose, Saeka Matsuhira, Tatiana Alexandrovna Batanova, Youn-Kyoung Goo, Mohamad A Terkawi, Yoshifumi Nishikawa, Katsuya Kitoh, Xuenan Xuan, Yasuhiro Takashima
The Journal of veterinary medical science, 71, 8, 1133, 6, Aug. 2009, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Characterization of a leucine aminopeptidase of Babesia gibsoni.
H Jia, M A Terkawi, G O Aboge, Y-K Goo, Y Luo, Y Li, J Yamagishi, Y Nishikawa, I Igarashi, C Sugimoto, K Fujisaki, X Xuan
Parasitology, 136, 9, 945, 52, 9, Aug. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular and immunological characterization of Babesia gibsoni and Babesia microti heat shock protein-70.
M Alaa Terkawi, G Aboge, H Jia, Y-K Goo, H Ooka, J Yamagishi, Y Nishikawa, N Yokoyama, I Igarashi, S-I Kawazu, K Fujisaki, X Xuan
Parasite immunology, 31, 6, 328, 40, 6, Jun. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Identification of secreted antigen 3 from Babesia gibsoni.
Honglin Jia, M Alaa Terkawi, Gabriel Oluga Aboge, Youn-Kyoung Goo, Liqing Ma, Jinlin Zhou, Yoshifumi Nishikawa, Ikuo Igarashi, Kozo Fujisaki, Xuenan Xuan
Clinical and vaccine immunology : CVI, 16, 6, 944, 8, 6, Jun. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Genetic diversity of two selected antigen loci in Babesia gibsoni Asian genotype obtained from Japan and Jeju island of South Korea.
Honglin Jia, Gabriel Oluga Aboge, M Alaa Terkawi, Youn-Kyoung Goo, Yoshifumi Nishikawa, Ken Kuriki, Kyoung-Kap Lee, Hyung-Kwan Jang, Suk Kim, Kozo Fujisaki, Xuenan Xuan
Veterinary parasitology, 162, 1-2, 142, 6, 26 May 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Characterization of the Babesia gibsoni 12-kDa protein as a potential antigen for the serodiagnosis.
Youn-Kyoung Goo, Honglin Jia, G Oluga Aboge, M Alaa Terkawi, Eung-goo Lee, Junya Yamagishi, Yoshifumi Nishikawa, Hyung-Kwan Jang, Fujiko Sunaga, Kazuhiko Namikawa, Kozo Fujisaki, Xuenan Xuan
Parasitology international, 58, 1, 55, 60, Mar. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cloning, expression, and characterization of Babesia gibsoni dihydrofolate reductase-thymidylate synthase: inhibitory effect of antifolates on its catalytic activity and parasite proliferation.
Gabriel O Aboge, Honglin Jia, Mohamad A Terkawi, Youn-Kyoung Goo, Yoshifumi Nishikawa, Fujiko Sunaga, Kuzuhiko Namikawa, Naotoshi Tsuji, Ikuo Igarashi, Hiroshi Suzuki, Kozo Fujisaki, Xuenan Xuan
Antimicrobial agents and chemotherapy, 52, 11, 4072, 80, Nov. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

C3 contributes to the cross-protective immunity induced by Babesia gibsoni phosphoriboprotein P0 against a lethal B. rodhaini infection
M. A. Terkawi, G. Zhang, H. Jia, G. Aboge, Y. K. Goo, Y. Nishikawa, N. Yokoyama, I. Igarashi, S. I. Kawazu, K. Fujisaki, X. Xuan
Parasite Immunology, 30, 6-7, 365, 370, 6-7, Jun. 2008, [Peer-reviewed]
English, Scientific journal

Babesia gibsoni: Serodiagnosis of infection in dogs by an enzyme-linked immunosorbent assay with recombinant BgTRAP.
Youn-Kyoung Goo, Honglin Jia, G Oluga Aboge, M Alaa Terkawi, Ken Kuriki, Chinatsu Nakamura, Akiko Kumagai, Jinlin Zhou, Eung-goo Lee, Yoshifumi Nishikawa, Ikuo Igarashi, Kozo Fujisaki, Xuenan Xuan
Experimental parasitology, 118, 4, 555, 60, 4, Apr. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

Babesia gibsoni: Identification of an immunodominant, interspersed repeat antigen
Honglin Jia, M. Alaa Terkawi, Gabriel Oluga Aboge, Youn-Kyoung Goo, Jinlin Zhou, Eung-Goo Lee, Yoshifumi Nishikawa, Ikuo Igarashi, Kozo Fujisaki, Xuenan Xuan
Experimental Parasitology, 118, 1, 146, 149, 1, Jan. 2008, [Peer-reviewed]
English, Scientific journal

A shared antigen among Babesia species: Ribosomal phosphoprotein P0 as a universal babesial vaccine candidate
M. Alaa Terkawi, Honglin Jia, Aboge Gabriel, Youn-Kyoung Goo, Yoshifumi Nishikawa, Naoaki Yokoyama, Ikuo Igarashi, Kozo Fujisaki, Xuenan Xuan
Parasitology Research, 102, 1, 35, 40, 1, Dec. 2007, [Peer-reviewed]
English, Scientific journal

A novel 57-kDa merozoite protein of Babesia gibsoni is a prospective antigen for diagnosis and serosurvey of canine babesiosis by enzyme-linked immunosorbent assay.
Gabriel Oluga Aboge, Honglin Jia, Mohamad Alaa Terkawi, Younkyoung Goo, Ken Kuriki, Yoshifumi Nishikawa, Ikuo Igarashi, Hiroshi Suzuki, Xuenan Xuan
Veterinary parasitology, 149, 1-2, 85, 94, 21 Oct. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Babesia gibsoni ribosomal phosphoprotein P0 induces cross-protective immunity against B. microti infection in mice.
M Alaa Terkawi, Honglin Jia, Jinlin Zhou, Eung-goo Lee, Ikuo Igarashi, Kozo Fujisaki, Yoshifumi Nishikawa, Xuenan Xuan
Vaccine, 25, 11, 2027, 35, 01 Mar. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

継代細胞における糖鎖シグネチャーの解明
宝満健太郎, 徳廣泰貴, 小野寺智洋, 江畑拓, ALAA Terkawi, 松岡正剛, 花松久寿, 古川潤一, 角家健, 岩崎倫政, 北海道整形災害外科学会, 143rd, 2024

網羅的遺伝子発現解析によるマクロファージに対する軟骨破片の影響の検討
濱崎雅成, TERKAWI Alaa, 小野寺智洋, 宝満健太郎, 菱村亮介, XU Liang, 宮崎拓自, TIAN Yuan, 岩崎倫政, 日本軟骨代謝学会プログラム・抄録集, 32nd, 118, Mar. 2019
Japanese

超高分子ポリエチレン摩耗粉によるヒトマクロファージの遺伝子発現変化は関節リウマチと類似する　　　　　　　　　　　　　　　
Terkawi Alaa, 濱崎 雅成, 高橋 大介, 角家 健, 浅野 毅, 入江 徹, 小野寺 智洋, 高畑 雅彦, 岩崎 倫政, 日本整形外科学会雑誌, 91, 8, S1722, S1722, Aug. 2017
(公社)日本整形外科学会, Japanese

国際獣疫事務局(OIE)馬ピロプラズマ症リファレンスラボラトリーの役割と活動
五十嵐郁男, TERKAWI Alaa, 玄学南, 横山直明, 日本獣医学会学術集会講演要旨集, 156th, 235, 30 Aug. 2013
Japanese

エジプトとケニアの牛および水牛より単離されたBabesia bovisとB.bigeminaの分子学的性状解析(Molecular characterizations of Babesia bovis and B. bigemina isolated from cattle and water buffalo in Egypt and Kenya)　　　　　　　　　　　　　　　
Moumouni Paul, Franck Adjou, Aboge Gabriel, Hany Ibrahim, Terkawi Alaa, 正谷 達謄, 曹 世諾, Kamyingkird Ketsarin, Moussa Ahmed, 西川 義文, 鈴木 宏志, 玄 学南, 日本獣医学会学術集会講演要旨集, 155回, 212, 212, Mar. 2013
(公社)日本獣医学会, English

寄生虫Babesia M17ロイシンアミノペプチダーゼの分子薬剤標的としての有効性の検証(Validating M17 leucine aminopeptidase of Babesia parasite as a molecular drug target)　　　　　　　　　　　　　　　
Aboge Gabriel Oluga, 曹 世諾, Terkawi Alaa, 正谷 達謄, 具 潤景, 横山 直明, 五十嵐 郁男, 西川 義文, 鈴木 宏志, 玄 学南, 日本獣医学会学術集会講演要旨集, 154回, 216, 216, Aug. 2012
(公社)日本獣医学会, English

Babesia gibsoni原虫の薬剤標的DHFR-TSの性状解析　　　　　　　　　　　　　　　
Aboge G, Jia Honglin, Terkawi A, Goo Y.K, 西川 義文, 須永 藤子, 並河 和彦, 五十嵐 郁男, 鈴木 宏志, 藤崎 幸蔵, 玄 学南, 獣医寄生虫学会誌, 7, 2, 91, 91, Dec. 2008
日本獣医寄生虫学会, English

Drug discovery against Babesia and Toxoplasma. (Apicomplexan Parasites: Molecular Approaches Toward Targeted Drug Development Drug Discovery in Infectious Diseases.　　　　　　　　　　　　　　　
Terkawi MA, Igarashi I
Wiley-VCH, Weinheim, 2011

Macrophages: A double-edged sword in aseptic loosening of total joint arthroplasty　　　　　　　　　　　　　　　
Alaa Terkawi
Asia Pacific Society for Biology and Medical Sciences (APSBMS), 29 Jul. 2019, English, Invited oral presentation
[Invited], [International presentation]

Macrophage and neutrophils, Friend or foe to our health? Journey through our immune system　　　　　　　　　　　　　　　
Alaa Terkawi
帯広畜産大学テニュアトラック研究成果発表会, 20 Jul. 2016, English
[Invited], [Domestic Conference]

Oct. 2021 - Present
Japan College of Rheumatology　　　　　　　　　　　　　　　

Oct. 2017 - Present
Japanese society for immunology　　　　　　　　　　　　　　　

Oct. 2016 - Present
Japanese society for biomaterials　　　　　　　　　　　　　　　

Oct. 2016 - Present
Japanese society for bone and mineral research　　　　　　　　　　　　　　　

Apr. 2016 - Present
HOSP　　　　　　　　　　　　　　　

Functional analysis of bone macrophages that control bone metabolism for the development of therapeutic drugs for osteoporosis.
Grants-in-Aid for Scientific Research
Apr. 2023 - Mar. 2026
照川 アラー
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23H03025

Towards therapeutic approach for musculoskeletal diseases in an aging society　　　　　　　　　　　　　　　
Mar. 2023 - Mar. 2025
Kobayashi Foundation, Principal investigator

炎症収束性貪食細胞由来細胞外小胞による関節炎収束メカニズムの解明　　　　　　　　　　　　　　　
Apr. 2020 - Mar. 2023
Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research C, Coinvestigator

抗炎症性マクロファージ由来因子と骨関連細胞に着目した新規骨粗鬆症メカニズムの解明.　　　　　　　　　　　　　　　
Apr. 2020 - Mar. 2023
Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research C, Coinvestigator

Communication between gut and osteal macrophages as a novel regulatory axis in bone homeostasis　　　　　　　　　　　　　　　
Dec. 2021 - Dec. 2022
Alaa Terkawi (Terukawa), Tatiana Milena Marques,
MIRAI2.0 – Joint seed funding of Japan-Sweden collaborative projects, Hokkaido University, Örebro University, Principal investigator

骨粗鬆症の新規治療薬として応用可能なOsteomacs (骨マクロファージ)由来因子の網羅的解析　　　　　　　　　　　　　　　
Jan. 2021 - Dec. 2022
Hirose Foundation, Principal investigator

培養細胞上の糖鎖抗原変化と自家細胞移植における免疫応答発生機序の解明　　　　　　　　　　　　　　　
Jun. 2019 - Mar. 2021
Grant-in-Aid for Challenging Research (Exploratory), Coinvestigator

Investigation of roles of the synovial macrophage-derived exosomes on the progression of osteoarthritis and rheumatoid arthritis　　　　　　　　　　　　　　　
Apr. 2018 - Mar. 2021
Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research C, Principal investigator

変形性関節症制圧を目指した新規免疫ネットワーク解析手法を用いた治療薬の開発　　　　　　　　　　　　　　　
Jun. 2017 - Mar. 2020
Grant-in-Aid for Challenging Research (Exploratory), Coinvestigator

複合細胞移植による新規末梢神経再生方法の開発　　　　　　　　　　　　　　　
Apr. 2017 - Mar. 2020
Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research C, Coinvestigator

人工股関節置換術後の骨溶解を制御する新規治療法の開発　　　　　　　　　　　　　　　
Grant-in-Aid for Scientific Research C
Apr. 2017 - Mar. 2019
Alaa Terkawi
Japan Society for the Promotion of Science, Principal investigator, Competitive research funding

炎症性骨溶解を制御する新規治療法の開発　　　　　　　　　　　　　　　
2018 - 2019
Akiyama Foundation Encouragement Grant, Principal investigator

Elucidation of mechanisms by which host immune cells kill protozoan parasites and development of antiparasitic peptide　　　　　　　　　　　　　　　
Grant-in-Aid for Young Scientists (B)
Apr. 2015 - Mar. 2017
Alaa Terkawi
Japan Society for the Promotion of Science, Principal investigator, Competitive research funding

破骨細胞分化抑制因子を含む骨粗鬆症治療剤　　　　　　　　　　　　　　　
Patent right, Alaa Terkawi
特願P2018-008, 09 Apr. 2018

抗原虫能を持つ合成ペプチド　　　　　　　　　　　　　　　
Patent right, Alaa Terkawi
特願2015-233632, Oct. 2015