江畑　拓 (エバタ　タク)

医学研究院　専門医学系部門　機能再生医学分野特任助教
Last Updated :2026/04/14

■研究者基本情報

Researchmap個人ページ

ホームページURL

研究者番号

  • 00962953

J-Global ID

研究キーワード

  • 整形外科学
  • スポーツ医学
  • 軟骨代謝

研究分野

  • ライフサイエンス, スポーツ科学
  • ライフサイエンス, 整形外科学

■経歴

学歴

  • 2018年04月 - 2022年03月, 北海道大学, 大学院 医学院
  • 2012年03月, 旭川医科大学, 医学部, 医学科

■研究活動情報

受賞

  • 2025年04月, 公益社団法人 整形災害外科学研究助成財団, 令和6年度研究助成 基礎的研究 財団賞　　　　　　　　　　　　　　　
    血小板由来細胞外小胞を用いた変形性関節症に対する革新的治療方法の開発
    江畑 拓
  • 2024年02月, 日本軟骨代謝学会, 第29回日本軟骨代謝学会賞　　　　　　　　　　　　　　　

論文

  • Epidemiological landscape and clinical heterogeneity of ultra-rare sarcomas: A population-based study from the SEER database.
    Ryuichi Fukuda, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Dai Sato, Taku Ebata, Hirokazu Shimizu, Eiji Kondo, Norimasa Iwasaki
    Cancer epidemiology, 102, 103055, 103055, 2026年03月24日, ［国際誌］
    英語, 研究論文（学術雑誌）, INTRODUCTION: Ultra-rare sarcomas (URS), defined by the Connective Tissue Oncology Society (CTOS) as subtypes with an incidence of ≤ 1 per 1000,000 individuals per year, present significant diagnostic and therapeutic challenges. This study aimed to elucidate the epidemiological landscape and clinical characteristics of URS using a large-scale population-based registry. METHODS: Patients diagnosed with bone sarcomas (BS) and soft tissue sarcomas (STS) between 2000 and 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cases were classified into URS and non-URS groups based on the CTOS definition. Patient demographics, tumor characteristics, and survival outcomes were analyzed. RESULTS: The collective incidence rates of bone (B-URS) and soft tissue URS (ST-URS) were 2 and 14 per 1000,000 respectively. Among 14,695 BS and 94,455 STS cases included, URS accounted for 3099 (21.1%) and 15,155 (16.0%). B-URS were more frequently diagnosed in older patients (≥40 years) and presented with lower pathological grades. Conversely, ST-URS were more common in younger patients and exhibited higher rates of metastases. A substantial proportion had unknown pathological grades (53.4% in B-URS; 35.9% in ST-URS), reflecting diagnostic complexity. Although survival analysis indicated outcomes for URS were comparable to or better than non-URS, this likely reflects the prevalence of indolent subtypes rather than superior treatment efficacy. CONCLUSION: This study provides a comprehensive epidemiological description of URS based on the CTOS definition. Our findings highlight the significant clinical heterogeneity of URS, characterized by indeterminate grading and diverse biological behaviors.
  • Return to sport outcomes after inverted V-shaped (IV) high tibial osteotomy were comparable to those after medial opening-wedge high tibial osteotomy, even though the IV cohort had more severe preoperative disease.
    Taku Ebata, Eiji Kondo, Koji Yabuuchi, Koji Iwasaki, Dai Sato, Masatake Matsuoka, Tomohiro Onodera, Kazunori Yasuda, Tomonori Yagi, Norimasa Iwasaki
    Journal of experimental orthopaedics, 13, 1, e70667, 2026年01月, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: The primary aim was to compare return to sport (RTS) outcomes following inverted V-shaped high tibial osteotomy (IV-HTO) versus medial opening-wedge (OW)-HTO for medial knee osteoarthritis (OA). The secondary aim was to compare patient-reported outcomes and radiographic parameters between the procedures. METHODS: This retrospective cohort study included patients who underwent HTO for medial knee OA between 2017 and 2022. Inclusion criteria were preoperative sports participation and 2-year follow-up. Patients were allocated to IV-HTO (IV group) or OW-HTO (OW group) according to indications based on the planned correction angle and patellofemoral OA grade. Outcomes were assessed preoperatively and at 2 years. Between-group comparisons used appropriate parametric/nonparametric tests, with p < 0.05 considered significant. RESULTS: A total of 107 patients were analysed (IV group: 54 patients; OW group: 53 patients). Mean age was 58.4 years, body mass index (BMI) 25.6 kg/m2 and follow-up 29.5 months. Preoperative femorotibial and patellofemoral Kellgren-Lawrence grades and varus deformity (% mechanical axis) were more severe in the IV group (both p < 0.001). RTS rates were 91% (49/54) in the IV group and 91% (48/53) in the OW group (p = 0.975), with mean time to RTS of 8.4 and 8.8 months, respectively (p = 0.523). Lysholm score and Knee Injury and Osteoarthritis Outcome Score (KOOS) improved significantly in both groups (all p < 0.001), with similar minimal clinically important difference (MCID) responder rates. From preoperative to postoperative assessments, OW-HTO increased posterior tibial slope (9.3 ± 2.3° to 10.2 ± 2.4°, p < 0.001), whole leg length (800 ± 59 to 808 ± 59 mm, p < 0.001) and decreased the Caton-Deschamps ratio (1.03 ± 0.13 to 0.88 ± 0.14, p < 0.001), whereas IV-HTO showed no significant changes (all p > 0.05). CONCLUSIONS: IV-HTO achieved RTS and patient-reported outcomes comparable to OW-HTO at 2 years in patients with more severe preoperative disease. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
  • Transcriptomic profiling reveals a dramatic inflammatory shift in osteal macrophages during colitis-induced osteoporosis.
    Ryota Suzuki, Liyile Chen, Tsutomu Endo, Taiki Tokuhiro, Masaya Nakajo, Yuki Ogawa, Hend Alhasan, Taku Ebata, Daisuke Takahashi, Ken Kadoya, Masahiko Takahata, Norimasa Iwasaki, M Alaa Terkawi
    Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74, 1, 165, 165, 2025年11月21日, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: Colitis disrupts the intestinal barrier, leading to increased permeability and the translocation of harmful microbial components into the circulation and distant organs, including bone. Given that macrophages serve as both frontline immune defenders in tissues and key regulators of bone homeostasis, this study investigates molecular alterations in osteal macrophages (Omacs) and their contribution to bone loss in a murine model of colitis-induced osteoporosis. METHODS: Colitis-induced osteoporosis was established by administering DSS in drinking water for 5 days. Omacs were isolated from bone tissue and subjected to bulk RNA-seq analysis, phagocytosis assays and co-culture models with osteoblasts or osteoclast precursors. RESULTS: RNA-seq data of Omcas demonstrated a shift towards an inflammatory phenotype under colitis conditions, which was accompanied by bone loss in mice. The upregulated genes in these cells were most significantly enriched in IL-17, NF-κB, and TNF signaling pathways. Importantly, these cells exhibited decreased phagocytic activity and were able to disrupt osteoblast differentiation and promote osteoclast differentiation in vitro. CONCLUSIONS: These results indicate that colitis triggers a significant inflammatory response in Omacs, which can contribute to bone metabolic dysfunction. Modulating the activation of inflammatory pathways may offer a potential therapeutic avenue for treating colitis-induced osteoporosis.
  • Characterization of time-dependent changes in the subchondral bone density distribution of the proximal tibia following high tibial osteotomy.
    Yoshiaki Hosokawa, Koji Iwasaki, Taku Ebata, Dai Sato, Masanari Hamasaki, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
    Journal of experimental orthopaedics, 12, 4, e70517, 2025年10月, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: This study aimed to evaluate the time-dependent changes in the medial and lateral subchondral bone density distribution of the tibial joint surface before and after high tibial osteotomy (HTO) using computed tomography-osteoabsorptiometry. METHODS: This study included 17 patients (20 knees) (8 men and 9 women; mean age: 55 years) who underwent HTO for medial compartment osteoarthritis. Computed tomography-osteoabsorptiometry was conducted to measure the subchondral bone density distribution in the tibial joint surface. The high-density area (HDA), defined as the region corresponding to the highest Hounsfield unit values that comprises 20% of the total region, was calculated. Medial ratio was defined as the proportion of the HDA in the medial compartment relative to the total HDA of both compartments. Measurements were performed preoperatively and at 3, 6, 12 and 24 months post-operatively, and a generalized linear regression analysis with a gamma distribution model was conducted. RESULTS: The medial ratios (mean ± standard deviation) were 89 ± 9% preoperatively, 73 ± 12% at 3 months, 78 ± 13% at 6 months, 78 ± 10% at 12 months and 77 ± 17% at 24 months. Based on the gamma distribution, the non-linear model was expressed as follows: Y = 82.8 × t - 0.04 × exp(-0.004 × t). This finding indicated that the medial ratio had a decreasing trend, reaching its minimum at 10.2 months post-operatively. CONCLUSION: This study showed time-dependent changes in the subchondral bone density on the tibial side after HTO. The changes in the bone density distribution on the medial and lateral tibial joint surface, which are associated with alignment correction, stabilized at approximately 10.5 months post-operatively. Therefore, the optimal timing for evaluating subchondral bone density in response to stress redistribution may be after 10.2 months. LEVEL OF EVIDENCE: Level IV.
  • Comparison of clinical features between patients with bone and soft tissue angiosarcomas.
    Yuta Kamo, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Dai Sato, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2025年09月05日, ［国内誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Angiosarcoma is a rare and aggressive malignancy arising from vascular endothelial cells, with distinct subtypes originating in bone (AS-B) and soft tissue (AS-ST). While these subtypes share pathological similarities, differences in clinical outcomes remain unclear due to limited data. This study aimed to compare the clinical features, treatment strategies, and survival outcomes between AS-B and AS-ST using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A retrospective analysis was conducted using the SEER database from 2000 to 2020. A total of 3600 angiosarcoma cases were included, with 114 AS-B and 3486 AS-ST cases. Patient demographics, tumor characteristics, and treatment modalities were analyzed. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier analysis, and risk factors were evaluated through Cox proportional hazards modeling. RESULTS: AS-B patients were predominantly male, with higher rates of extremity tumors and distant metastases compared to AS-ST. The 5-year CSS was 34.4 % and OS was 15.0 % for AS-B, compared to 38.3 % CSS and 26.0 % OS for AS-ST, with no significant differences after Cox proportional hazards modeling. Metastases were associated with poorer survival in AS-B, while surgical intervention and chemotherapy improved both CSS and OS. Similar trends were observed in AS-ST, with tumor grade, metastases, and treatment modalities influencing survival. CONCLUSION: This population-based study highlights the distinct clinical features of AS-B and AS-ST. It also demonstrates comparable survival outcomes between the two groups. Although survival was similar between AS-B and AS-ST, their distinct clinical characteristics suggest the need for site-specific therapeutic considerations. Given the retrospective design, observed treatment effects should be interpreted as associations rather than causal relationships.
  • 内側開大式高位脛骨骨切り術前後の脛骨関節面軟骨下骨骨密度分布の変化と術後臨床成績との関連性
    江畑 拓, 岩崎 浩司, 佐藤 大, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 8, S1720, S1720, (公社)日本整形外科学会, 2025年09月
    日本語
  • 筋骨格シミュレーションを用いた脛骨関節面傾斜と脛骨関節面荷重の関係についての検討
    土橋 晋也, 岩崎 浩司, 佐橋 健人, 細川 吉暁, 江畑 拓, 松岡 正剛, 小野寺 智洋, 近藤 英司, 遠山 晴一, 岩崎 倫政
    日本整形外科学会雑誌, 99, 8, S1806, S1806, (公社)日本整形外科学会, 2025年09月
    日本語
  • 高位脛骨切り術における,術前MRIを用いた質的評価による臨床成績に及ぼす影響の検討
    佐藤 大, 趙 淵石, 江畑 拓, 細川 吉暁, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 8, S1829, S1829, (公社)日本整形外科学会, 2025年09月
    日本語
  • AIを用いた下肢アライメント計測システムの確立
    中條 誠也, 岩崎 浩司, 細川 吉暁, 江畑 拓, 佐藤 大, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 8, S1927, S1927, (公社)日本整形外科学会, 2025年09月
    日本語
  • Meniscus extrusion and lower leg alignment predict the distribution of subchondral bone density across the knee joint.
    Koji Iwasaki, Taku Ebata, Tomoya Sato, Yoshiaki Hosokawa, Masanari Hamasaki, Dai Sato, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
    The Knee, 57, 68, 76, 2025年08月19日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Stress distribution is the pattern of mechanical load distribution, particularly between the medial and lateral compartments. Lower leg alignment and the meniscus play an important role in this distribution. CT-osteoabsorptiometry estimates stress distribution by analyzing the distribution pattern of subchondral bone density. This study aimed to explore the extent to which lower limb alignment and meniscal extrusion can explain the distribution of subchondral bone density. METHODS: This was a retrospective study including 92 patients (73 with osteoarthritis (OA) and 19 without OA). Lower limb alignment, meniscus-extrusion ratio (MER), and subchondral bone density were assessed using CT-osteoabsorptiometry. High-density areas (HDA) on the articular surface were quantitatively analyzed. RESULTS: Hip-knee-ankle (HKA) angle, medial MER (MMER), lateral MER (LMER), and medial compartment HDA to total HDA ratio (medial ratio) were -4.3°, 46.8 %, 20.4 %, and 70.0 %, respectively. Multiple regression analysis revealed that HKA, MMER, and LMER were significant variables. The adjusted R2 of HKA, MMER, and LMER for the medial ratio was 0.80. The standardized coefficients for HKA, MMER, and LMER were -0.30, 0.40, and -0.41, respectively. CONCLUSIONS: Lower leg alignment and meniscus extrusion explain 80% of the variance in the distribution of subchondral bone density. These findings indicate that both factors can account for approximately 80% of the estimated stress distribution as assessed by CT-osteoabsorptiometry. The distribution of subchondral bone density estimated by HKA and meniscus extrusion was useful for diagnosing and treating knee osteoarthritis.
  • 再生医療 モチジェル(高純度硬化性ゲル)の再生医療応用と製品化の進展　　　　　　　　　　　　　　　
    小野寺 智洋, 岩崎 浩司, 松岡 正剛, 江畑 拓, 佐藤 大, 原 健人, 近藤 英司, 門間 太輔, 鈴木 孝治, 井上 雅之, 岩崎 倫政
    東日本整形災害外科学会雑誌, 37, 3, 177, 177, 東日本整形災害外科学会, 2025年08月
    日本語
  • 筋骨格シミュレーションを用いた脛骨関節面傾斜と脛骨関節面荷重の関係についての検討　　　　　　　　　　　　　　　
    土橋 晋也, 岩崎 浩司, 佐橋 健人, 原 健人, 佐藤 大, 江畑 拓, 松岡 正剛, 小野寺 智洋, 近藤 英司, 遠山 晴一, 岩崎 倫政
    東日本整形災害外科学会雑誌, 37, 3, 292, 292, 東日本整形災害外科学会, 2025年08月
    日本語
  • The Relationship of Meniscal Extrusion to Subchondral Bone Density in Medial Knee Osteoarthritis.
    Taku Ebata, Koji Iwasaki, Tomoya Sato, Yoshiaki Hosokawa, Masanari Hamasaki, Dai Sato, Masatake Matsuoka, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki
    Orthopaedic journal of sports medicine, 13, 8, 23259671251366424, 23259671251366424, 2025年08月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The hoop function of the meniscus plays a crucial role in stress distribution across the knee joint. While medial meniscal extrusion is known to contribute to the progression of medial knee osteoarthritis (OA) by altering load distribution within the knee joint, its exact effect on living humans remains unclear. PURPOSE: To investigate the influence of meniscal extrusion on subchondral bone density distribution in patients with medial knee OA. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This retrospective study included 59 patients with medial knee OA (OA group) and 19 control participants (non-OA group). Radiographic parameters, including the hip-knee-ankle angle (HKA) and meniscal extrusion ratio (MER), were assessed. The subchondral bone density was evaluated using computed tomography-osteoabsorptiometry to analyze the high-density area (HDA) in the medial and lateral compartments on the articular surface of the proximal tibia. Correlations between these parameters were assessed using single and multiple regression analyses, with subgroup analysis conducted in OA patients with and without meniscal tears. RESULTS: In the OA group, the HKA, medial MER (MMER), and the ratio of the medial compartment HDA to the total HDA (medial ratio) were -7.4°, 64.8%, and 81.8%, respectively. In the non-OA group, these values were -2.1°, 12.5%, and 62.0%. Simple regression analysis showed that, in the OA group, the medial ratio was correlated with HKA (R 2 = 0.216; P < .001) and MMER (R 2 = 0.307; P < .001). Among non-OA participants, only MMER was correlated with the medial ratio (R 2 = 0.217; P = .045). The multivariable regression analysis demonstrated an adjusted R 2 value of 0.38 (P < .001) in the OA group. The standardized coefficients were 0.465 for MMER and -0.340 for HKA. Subgroup analysis further indicated that meniscal injury in OA patients amplified the effect of extrusion on subchondral bone density distribution, with an adjusted R 2 of 0.54 in the meniscal tear group. CONCLUSION: MMER had a greater influence on the mediolateral distribution of subchondral bone density in patients with medial knee OA than lower limb alignment, suggesting that the hoop function of the meniscus plays a more important role in altering stress distribution than leg alignment.
  • AYA世代における悪性骨・軟部腫瘍の年次発生率 米国National Childhood Cancer Registryを用いた研究
    松岡 正剛, 小野寺 智洋, 岩崎 浩司, 佐藤 大, 江畑 拓, 清水 寛和, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 6, S1355, S1355, (公社)日本整形外科学会, 2025年06月
    日本語
  • 血管肉腫における軟部組織発生腫瘍と骨発生腫瘍の比較 米国SEERデータベースを用いた研究
    加茂 雄太, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 佐藤 大, 江畑 拓, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 6, S1357, S1357, (公社)日本整形外科学会, 2025年06月
    日本語
  • Lateral Meniscal Cyst Diagnosed After Acute Onset of Common Peroneal Nerve Palsy.
    Mako Okumura, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Riku Miyaishi, Dai Sato, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
    Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews, 9, 6, 2025年06月01日, ［国際誌］
    英語, 研究論文（学術雑誌）, Common peroneal nerve palsy is often caused by compression at the fibular head, with ganglion cysts being the most common etiology. Although rare, meniscal cysts can also compress the nerve. We report a case of common peroneal nerve palsy due to a lateral meniscal cyst, successfully treated with surgery. A 38-year-old man presented with progressive pain and numbness in the right lateral knee and foot, along with difficulty dorsiflexing the ankle without any apparent history of trauma. Examination revealed a palpable mass on the lateral knee and sensory deficits in the superficial peroneal nerve distribution. Magnetic resonance imaging demonstrated a cystic lesion originating from the lateral meniscus. Nerve conduction studies showed reduced conduction velocity, confirming a diagnosis of common peroneal nerve palsy secondary to a lateral meniscal cyst. The patient underwent surgical excision of the cyst and arthroscopic meniscal repair. Intraoperatively, the cyst was compressing the common peroneal nerve. Postoperatively, motor function recovered over 1 year, with minor residual sensory deficits. No recurrence was observed at 1-year follow-up. Lateral meniscal cysts are a rare cause of common peroneal nerve palsy. Early diagnosis and surgical intervention can prevent permanent nerve damage and ensure functional recovery.
  • 両脚立位下肢全長X線の足の幅が関節面傾斜(JLO)に与える影響について
    中條 誠也, 岩崎 浩司, 近藤 英司, 小野寺 智洋, 松岡 正剛, 江畑 拓, 佐藤 大, 細川 吉暁
    日本整形外科学会雑誌, 99, 2, S14, S14, (公社)日本整形外科学会, 2025年03月
    日本語
  • 本邦外反母趾診療ガイドラインとの比較による対話型オープンAIの検討
    松岡 正剛, 小野寺 智洋, 岩崎 浩司, 佐藤 大, 江畑 拓, 細川 吉暁, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S142, S142, (公社)日本整形外科学会, 2025年03月
    日本語
  • 膝関節面の軟骨下骨の骨密度分布に半月板逸脱と下肢アライメントが与える影響
    岩崎 浩司, 江畑 拓, 佐藤 知哉, 細川 吉暁, 佐藤 大, 鈴木 裕貴, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S284, S284, (公社)日本整形外科学会, 2025年03月
    日本語
  • 脛骨近位骨切り術後の脛骨関節面軟骨下骨骨密度分布の変化
    細川 吉暁, 岩崎 浩司, 江畑 拓, 佐藤 大, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S284, S284, (公社)日本整形外科学会, 2025年03月
    日本語
  • 膝関節再生医療の現状と課題 バイオマテリアルを用いた軟骨再生治療の低侵襲化の試みと未来への展望
    小野寺 智洋, 岩崎 浩司, 松岡 正剛, 江畑 拓, 佐藤 大, 細川 吉暁, 近藤 英司, 門間 太輔, 鈴木 孝治, 井上 雅之, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S377, S377, (公社)日本整形外科学会, 2025年03月
    日本語
  • 逆V字型高位脛骨切り術における,術前MRIを用いた質的評価による臨床成績に及ぼす影響の検討
    趙 淵石, 佐藤 大, 江畑 拓, 細川 吉暁, 岩崎 浩司, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S402, S402, (公社)日本整形外科学会, 2025年03月
    日本語
  • 下肢OAの病態を再考する 下肢アライメントと半月板から見た膝関節の応力分布
    岩崎 浩司, 江畑 拓, 佐藤 知哉, 細川 吉暁, 佐藤 大, 松岡 正剛, 前田 龍智, 小野寺 智洋, 大越 康充, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 2, S435, S435, (公社)日本整形外科学会, 2025年03月
    日本語
  • 高純度硬化性アルギン酸ゲルを用いた膝関節軟骨損傷に対する低侵襲軟骨再生治療の中期成績
    細川 吉暁, 小野寺 智洋, 坂本 圭太, 江畑 拓, 佐藤 大, 松岡 正剛, 岩崎 浩司, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 3, S699, S699, (公社)日本整形外科学会, 2025年03月
    日本語
  • Atypical lipomatous tumor/well differentiated liposarcomaの脱分化
    松岡 正剛, 小野寺 智洋, 岩崎 浩司, 佐藤 大, 江畑 拓, 細川 吉暁, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 3, S703, S703, (公社)日本整形外科学会, 2025年03月
    日本語
  • 四肢原発非円形細胞肉腫において診断確定から治療開始までの期間が生存に与える影響 米国SEERデータベースを用いた研究
    高橋 桜子, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 佐藤 大, 江畑 拓, 細川 吉暁, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 3, S810, S810, (公社)日本整形外科学会, 2025年03月
    日本語
  • 内側型変形性膝関節症患者の内側半月板逸脱が脛骨関節面軟骨下骨骨密度分布に及ぼす影響
    江畑 拓, 岩崎 浩司, 佐藤 知哉, 細川 吉暁, 佐藤 大, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 99, 3, S1094, S1094, (公社)日本整形外科学会, 2025年03月
    日本語
  • Survival outcomes in non-operative cases of localized extremity sarcoma.
    Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
    Surgical oncology, 58, 102181, 102181, 2025年02月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Soft-tissue sarcomas (STSs) are a diverse group of malignancies challenging to treat when surgery is not an option. The aim of this study was to investigate the survival of non-surgical cases in STSs, and to examine the impact of radiation therapy (RT) on survival within this group of cases. METHODS: Utilizing the SEER database, we conducted a retrospective cohort study of localized extremity non-small round cell sarcoma diagnosed between 2000 and 2019. A total of 444 non-operative cases were identified and analyzed for cancer-specific survival (CSS) and overall survival (OS) using Kaplan-Meier and Cox proportional hazards models. RESULTS: Among the non-operative cohort, the median age at diagnosis was 72 years. The median survival was 10 months, with AJCC 8th edition clinical stage-specific 5-year CSS rates of 80 % for Stage 1B, 53 % for Stage 2, 47 % for Stage 3A, and 22 % for Stage 3B. The 5-year OS rates were 56 % for Stage 1B, 31 % for Stage 2, 26 % for Stage 3A, and 14 % for Stage 3B. Nearly half of the patients received RT, which was more prevalent in higher clinical stages. RT was associated with improved survival rates for both CSS and OS in patients who are unable to undergo surgical intervention. CONCLUSIONS: RT is associated with improved survival in non-operative localized extremity non-small round cell sarcoma patients. These insights are vital for clinical decision-making, emphasizing the need for personalized, non-surgical interventions to improve outcomes for patients where surgery is not feasible.
  • 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, 2025年01月14日, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
  • 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, M Alaa Terkawi, Norimasa Iwasaki
    Journal of autoimmunity, 149, 103334, 103334, 2024年12月, ［国際誌］
    英語, 研究論文（学術雑誌）, Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues. Given that CCN3 is highly expressed in RA joints and that its level is associated with the severity of the disease, we explored its molecular function in joints and therapeutic potential in RA. An analysis of public scRNA-seq data from the RA synovium revealed that CCN3 is expressed by an inflammatory fibroblast subset. Interestingly, stimulation with CCN3 resulted in the activation of the senescence pathway in synoviocytes and osteoclast differentiation in monocytes in vitro. Consistent with these results, the administration of CCN3 into the knee joint and onto the calvarial bone resulted in increased numbers of senescent synoviocytes in the joint and osteoclasts in the bone, respectively. Furthermore, the therapeutic potential of targeting CCN3 was evaluated in an experimental RA model. Administration of the CCN3 antibody significantly suppressed inflammation and osteoclast numbers in the joints of the RA model mice. Our findings suggest that CCN3 contributes to pathological processes in RA and represents a promising therapeutic target for the treatment of RA.
  • 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, 2024年11月27日, ［国際誌］
    英語, 研究論文（学術雑誌）, 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, 2024年11月25日
    研究論文（学術雑誌）, 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, 2024年10月31日, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
  • Evaluating the Alignment of Artificial Intelligence-Generated Recommendations With Clinical Guidelines Focused on Soft Tissue Tumors.
    Masatake Matsuoka, Tomohiro Onodera, Ryuichi Fukuda, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
    Journal of surgical oncology, 2024年09月05日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The integration of artificial intelligence (AI), particularly, in oncology, has significantly shifted the paradigms of medical diagnostics and treatment planning. However, the utility of AI, specifically OpenAI's ChatGPT, in soft tissue sarcoma treatment, remains unclear. METHODS: We evaluated ChatGPT's alignment with the Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020. Twenty-two clinical questions (CQs) were formulated to encompass various aspects of sarcoma diagnosis, treatment, and management. ChatGPT's responses were classified into "Complete Alignment," "Partial Alignment," or "Nonalignment" based on the recommendation and strength of evidence. RESULTS: ChatGPT demonstrated an 86% alignment rate with the JOA guidelines. The AI provided two instances of complete alignment and 17 instances of partial alignment, indicating a strong capability to match guideline criteria for most questions. However, three discrepancies were identified in areas concerning the treatment of atypical lipomatous tumors, perioperative chemotherapy for synovial sarcoma, and treatment strategies for elderly patients with malignant soft tissue tumors. Reassessment with guideline input led to some adjustments, revealing both the potential and limitations of AI in complex sarcoma care. CONCLUSION: Our study demonstrates that AI, specifically ChatGPT, can align with clinical guidelines for soft tissue sarcoma treatment. It also underscores the need for continuous refinement and cautious integration of AI in medical decision-making, particularly in the context of treatment for soft tissue sarcoma.
  • 四肢原発非軟部肉腫におけるtime to treatment initiation解析
    高橋 桜子, 松岡 正剛, 小野寺 智洋, 岩崎 浩司, 濱崎 雅成, 江畑 拓, 細川 吉暁, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1748, S1748, (公社)日本整形外科学会, 2024年09月
    日本語
  • 内側型変形性膝関節症患者の半月板逸脱と脛骨関節面軟骨下骨骨密度分布との関連性 非変形性膝関節症患者との比較
    江畑 拓, 岩崎 浩司, 細川 吉暁, 濱崎 雅成, 松岡 正剛, 小野寺 智洋, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1771, S1771, (公社)日本整形外科学会, 2024年09月
    日本語
  • 高純度硬化性アルギン酸ゲルを用いた低侵襲軟骨再生治療の長期成績
    細川 吉暁, 小野寺 智洋, 江畑 拓, 濱崎 雅成, 松岡 正剛, 岩崎 浩司, 坂本 圭太, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1935, S1935, (公社)日本整形外科学会, 2024年09月
    日本語
  • 足部発生悪性骨腫瘍の生存解析 米国SEER databaseを用いた6541例による検討
    松岡 正剛, 小野寺 智洋, 岩崎 浩司, 濱崎 雅成, 江畑 拓, 細川 吉暁, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1966, S1966, (公社)日本整形外科学会, 2024年09月
    日本語
  • 好中球由来細胞外小胞は,secreted frizzled related protein 5により軟骨変性を抑制する
    北原 圭太, 照川 アラー, 江畑 拓, 清水 智弘, 遠藤 努, 浅野 毅, 高橋 大介, 角家 健, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1936, S1936, (公社)日本整形外科学会, 2024年09月
    日本語
  • 変形性膝関節症における血清中N型糖鎖バイオマーカーの網羅的解析
    小野寺 智洋, 宝満 健太郎, 花松 久寿, 古川 潤一, 岩崎 浩司, 松岡 正剛, 濱崎 雅成, 江畑 拓, 坂本 圭太, 近藤 英司, 岩崎 倫政
    日本整形外科学会雑誌, 98, 8, S1768, S1768, (公社)日本整形外科学会, 2024年09月
    日本語
  • 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, 2024年09月
    日本語
  • Amputation surgery associated with shortened survival in patients with localized extremity bone sarcoma.
    Nayuhito Yanagisawa, Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Eiji Kondo, Norimasa Iwasaki
    Journal of orthopaedics, 54, 124, 130, 2024年08月, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: This study assesses survival rates among patients with localized extremity bone sarcoma who have undergone amputation, pinpointing subpopulations that are disproportionately affected by amputation-related survival disparities. METHODS: Examination of data was conducted using the Surveillance, Epidemiology, and End Results (SEER) program, analyzing records of 3765 patients diagnosed with localized extremity bone sarcoma between 2000 and 2019. Of these, 857 received amputations (Amputation cohort), and 2908 underwent limb-sparing surgeries. Propensity score matching, considering demographic and clinical features, was utilized to ensure a fair comparison. RESULTS: Following propensity score matching, the study focused on 1714 cases. The Amputation cohort was observed to have significantly poorer survival rates (Cancer-Specific Survival [CSS]: Hazard Ratio [HR] = 1.28, 95% Confidence Interval [CI]: 1.05-1.55; Overall Survival [OS]: HR = 1.37, 95% CI: 1.15-1.63). Subsequent subgroup analysis indicated that individuals with tumors exceeding 8 cm in size or those located in the lower limbs were notably at a higher risk of shortened survival (for tumors >8 cm - CSS: HR = 1.32, 95% CI: 1.02-1.71; OS: HR = 1.39, 95% CI: 1.09-1.76; for lower limb tumors - CSS: HR = 1.25, 95% CI: 1.01-1.54; OS: HR = 1.33, 95% CI: 1.11-1.61). CONCLUSIONS: Our findings demonstrate that patients diagnosed with localized extremity bone sarcoma undergoing amputation exhibit lower survival rates, especially in cases involving tumors of greater size or those situated in the lower limbs. In patient groups where amputation is inevitable, careful follow-up is required after surgical intervention.
  • Radiation therapy improves survival in elderly patients with localized extremity soft tissue sarcoma.
    Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki
    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2024年07月15日, ［国内誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: This study aims to evaluate the efficacy of radiation therapy in enhancing survival outcomes among elderly patients diagnosed with localized extremity soft tissue sarcomas (STSs). Furthermore, it seeks to explore whether the survival benefits conferred by radiation therapy differ according to tumor characteristics and treatment modalities. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database to identify patients aged 80 years and older diagnosed with localized extremity STSs. The study assessed 1498 eligible patients, analyzing cancer-specific survival (CSS) and overall survival (OS) through Kaplan-Meier survival analysis and Cox proportional hazards modeling. Propensity score matching was employed to adjust for potential confounders. RESULTS: Among the analyzed patients, 773 patients underwent radiation therapy (Radiation group), while 725 patients either did not receive radiation therapy or it was unknown if they had (No-Radiation group). The 5-year OS rate was 40% in the radiation group compared to 38% in the no-radiation group. After propensity score matching, radiation therapy was associated with a significant improvement in OS (P = 0.005, HR = 0.8, 95% CI 0.7-0.9). Subgroup analyses indicated that patients undergoing primary tumor resection benefited most from radiation therapy in terms of OS. CONCLUSION: Radiation therapy is associated with improved overall survival in elderly patients with localized extremity STSs. These findings suggest that radiation therapy should be considered as a key component of the treatment strategy for this patient population, taking into account individual patient characteristics and comorbidities.
  • 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, 42, 5, 538, 550, Springer Science and Business Media LLC, 2024年06月08日, ［国内誌］
    英語, 研究論文（学術雑誌）, 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.
  • Analysis of foot-originating malignant bone tumors: Epidemiology, characteristics, and survival outcomes.
    Masatake Matsuoka, Tomohiro Onodera, Koji Iwasaki, Masanari Hamasaki, Taku Ebata, Yoshiaki Hosokawa, Ryuichi Fukuda, Eiji Kondo, Norimasa Iwasaki
    Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons, 2024年05月29日, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: The study examines the characteristics and outcomes of foot-originating malignant bone tumors via Surveillance Epidemiology and End Results (SEER) database analysis. METHODS: A retrospective review of 14,695 malignant bone tumor cases from 2000 to 2019 was conducted. RESULTS: Of the eligible cases, 147 (2.3 %) were foot-origin tumors, typically smaller and more commonly treated with surgery than those in other locations. These tumors were more frequently treated with surgical resection, with a higher proportion undergoing amputation. In contrast, foot-origin tumors were less often managed with chemotherapy and radiation. Foot-origin tumors exhibited higher survival rates compared to non-foot-origin tumors as shown in univariate analysis, although multivariate analysis did not reflect significant differences. CONCLUSION: Foot-originating malignant bone tumors tend to be smaller and are frequently surgically treated, correlating with favorable survival outcomes. These findings point to early detection as a potential factor in the improved survival rates, not necessarily the tumor's origin.
  • 炎症収束型好中球由来細胞外小胞は、secreted frizzled related protein 5により軟骨変性を抑制する
    北原 圭太, 江畑 拓, 西田 善郎, 塩田 惇喜, 徳廣 泰貴, 小川 裕生, 小川 拓也, 清水 智弘, 遠藤 努, 浅野 毅, 高橋 大介, 角家 健, 照川 アラー, 岩崎 倫政
    北海道整形災害外科学会雑誌, 66, 143rd suppl, 23, 23, 北海道整形災害外科学会, 2024年
    日本語
  • 急速破壊型股関節症の新規病態解明について インフラマソーム活性化による滑膜炎の関与
    横田 隼一, 清水 智弘, 松前 元, 江畑 拓, 照川 ヘンド, 高橋 大介, 照川 アラー, 岩崎 倫政
    北海道整形災害外科学会雑誌, 65, 2, 68, 78, 北海道整形災害外科学会, 2024年
    日本語
  • 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年
    日本語
  • Noncanonical Pyroptosis Triggered by Macrophage‐Derived Extracellular Vesicles in Chondrocytes Leading to Cartilage Catabolism in Osteoarthritis
    Taku Ebata, Mohamad Alaa Terkawi, Keita Kitahara, Shunichi 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, 75, 8, 1358, 1369, Wiley, 2023年06月04日
    研究論文（学術雑誌）, Objective

    The severity of osteoarthritis (OA) and cartilage degeneration is 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. We undertook this study to explore the pathologic role of inflammatory macrophage extracellular vesicles (EVs) in cartilage degeneration.

    Methods

    Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages, and the resulting EVs were harvested for chondrocyte stimulation in vitro and for intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA‐sequencing analysis and other functional assays. The action of caspase 11 was disrupted in vitro using a specific small interfering RNA or wedelolactone, and in experimental murine OA models by intraarticular injection of wedelolactone.

    Results

    Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA‐sequencing analyses of stimulated chondrocytes indicated that up‐regulated genes were mainly categorized into apoptotic process and tumor necrosis factor signaling pathways, 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 pathologic changes in collagenase‐induced and joint instability–induced OA models.

    Conclusion

    Our results provide new insight into the pathologic mechanisms of OA and suggest that noncanonical pyroptosis in chondrocytes represents an attractive therapeutic target for treatment.

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  • Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis
    Hend Alhasan, Mohamad Alaa Terkawi, Gen Matsumae, Taku Ebata, Yuan Tian, Tomohiro Shimizu, Yoshio Nishida, Shunichi Yokota, Fayna Garcia-Martin, Mahmoud M. Abd Elwakil, Daisuke Takahashi, Mahmoud A. Younis, Hideyoshi Harashima, Ken Kadoya, Norimasa Iwasaki
    Nature Communications, 13, 1, Springer Science and Business Media LLC, 2022年07月07日
    研究論文（学術雑誌）, Abstract

    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, 1109, 1109, MDPI AG, 2022年05月10日
    研究論文（学術雑誌）, 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.
  • 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, 2022年05月
    研究論文（学術雑誌）
  • Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris
    Gen Matsumae, Hiroaki Kida, Daisuke Takahashi, Tomohiro Shimizu, Taku Ebata, Shunichi Yokota, Hend Alhasan, Mahmoud Khamis Aly, Tomoyo Yutani, Keita Uetsuki, Mohamad Alaa Terkawi, Norimasa Iwasaki
    Journal of Biomedical Materials Research Part B: Applied Biomaterials, 110, 7, 1587, 1593, Wiley, 2022年02月05日
    研究論文（学術雑誌）, Abstract

    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.
  • Rheumatoid arthritis is a risk factor for refracture in patients with fragility fractures
    Hotaka Ishizu, Hirokazu Shimizu, Tomohiro Shimizu, Taku Ebata, Yuki Ogawa, Masahiro Miyano, Kosuke Arita, Yusuke Ohashi, Norimasa Iwasaki
    Modern Rheumatology, 32, 6, 1017, 1022, Oxford University Press (OUP), 2021年12月03日
    研究論文（学術雑誌）, ABSTRACT

    Objectives

    To determine whether patients with rheumatoid arthritis (RA) who have had fragility fractures are at an increased risk of refractures.

    Methods

    Patients with fragility fractures who were treated surgically at 10 hospitals from 2008 to 2017 and who underwent follow-up for &gt;24 months were either categorized into a group comprising patients with RA or a group comprising patients without RA (controls). The groups were matched 1:1 by propensity score matching. Accordingly, 240 matched participants were included in this study. The primary outcome was the refracture rate in patients with RA as compared to in the controls. Multivariable analyses were also conducted on patients with RA to evaluate the odds ratios (ORs) for the refracture rates.

    Results

    Patients with RA were significantly associated with increased rates of refractures during the first 24 months (OR: 2.714, 95% confidence interval [95% CI]: 1.015–7.255; p = 0.040). Multivariable analyses revealed a significant association between increased refracture rates and long-term RA (OR: 6.308, 95% CI: 1.195–33.292; p = 0.030).

    Conclusions

    Patients with RA who have experienced fragility fractures are at an increased risk of refractures. Long-term RA is a substantial risk factor for refractures.
  • 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, 2021年12月
    研究論文（学術雑誌）
  • 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, 2021年08月
    日本語
  • Targeting thymidine phosphorylase as a potential therapy for bone loss associated with 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, Wiley, 2021年06月08日
    研究論文（学術雑誌）, Abstract

    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, 2021年06月
    研究論文（学術雑誌）
  • 急速破壊型股関節症におけるインフラマソームによる滑膜炎関与の検証
    横田 隼一, 清水 智弘, 松前 元, 江畑 拓, Alhasan Hend, 高橋 大介, Terkawi Alaa, 岩崎 倫政
    北海道整形災害外科学会雑誌, 63, 140th suppl, 8, 8, 北海道整形災害外科学会, 2021年
    日本語
  • 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
    Alhasan Hend, 松前 元, 江畑 拓, 横田 隼一, 清水 智弘, 高橋 大介, Terkawi Alaa, 岩崎 倫政
    北海道整形災害外科学会雑誌, 63, 140th suppl, 14, 14, 北海道整形災害外科学会, 2021年
    日本語
  • 炎症性マクロファージ由来細胞外小胞が軟骨変性に及ぼす影響
    江畑 拓, Alaa Terkawi, 松前 元, 横田 隼一, Hend Alhasan, 本谷 和俊, 清水 智弘, 高橋 大介, 小野寺 智洋, 角家 健, 岩崎 倫政
    北海道整形災害外科学会雑誌, 63, 140th suppl, 62, 62, 北海道整形災害外科学会, 2021年
    日本語
  • 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, Frontiers Media SA, 2020年08月04日, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
  • 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, Springer Science and Business Media LLC, 2020年05月05日
    研究論文（学術雑誌）, Abstract

    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.

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