Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation
Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation
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DOI：
10.1016/j.joca.2019.03.008
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发表时间：
2019-08-01
影响因子：
7
通讯作者：
Kanemura, N.
中科院分区：
文献类型：
--
作者：
Murata, K.;Kokubun, T.;Kanemura, N.
目的：关节异常不稳定导致软骨损伤和骨赘形成。我们研究了控制关节不稳定是否抑制慢性滑膜炎症和延迟骨赘形成，并研究了转化生长因子-β（TGF-β）信号在相关mechanism.Design中的作用：大鼠（n = 94）进行前交叉韧带（ACL）横断。胫骨前不稳定要么得到控制（CAM组），要么允许继续（SHAM组）。在2，4，8周手术后，放射学，组织病理学，免疫组化，免疫荧光，酶联免疫吸附试验检查进行评估骨赘形成和TGF-β signaling.Results：关节不稳定增加软骨退变评分和骨赘形成，细胞增生和增殖，滑膜增厚观察。主要发现是滑膜、关节软骨和胫骨后生长板中TGF-β表达和TGF-β磷酸化后Smad 2/3增加。（采用ELISA法测定TGF-β表达：4周; P = 0.009，95% CI [260.1-1340.0]）（p-Smad 2/3表达密度：4周; P = 0.024，95% CI [1.67-18.27]，8周; P = 0.034，95% CI [1.25-25.34]）。结论：胫骨前不稳定引起胫骨后段及滑膜TGF表达水平的变化，可能与骨赘形成有关。(C)2019国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-beta) signaling in the associated mechanism.Design: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-beta signaling.Results: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-beta expression and Smad2/3 following TGF-beta phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-beta expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model.Conclusions: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.