Department of Physical Therapy, School of Health and Social Services, Saitama Prefectural University, Saitama, Japan.
Department of Rehabilitation, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan.
Osteoarthritis Cartilage. 2019 Aug;27(8):1185-1196. doi: 10.1016/j.joca.2019.03.008. Epub 2019 Apr 23.
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-β) signaling in the associated mechanism.
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-β signaling.
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-β expression and Smad2/3 following TGF-β phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-β 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.
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.
关节不稳会导致软骨损伤和骨赘形成。我们研究了控制关节不稳是否能抑制慢性滑膜炎症和延迟骨赘形成，并探讨了转化生长因子-β（TGF-β）信号通路在相关机制中的作用。
大鼠（n=94）行前交叉韧带（ACL）切断术。胫骨前不稳定通过控制（CAM 组）或不控制（SHAM 组）来实现。术后 2、4、8 周，进行影像学、组织病理学、免疫组织化学、免疫荧光和酶联免疫吸附试验检查，评估骨赘形成和 TGF-β信号通路。
关节不稳增加了软骨退变评分和骨赘形成，并观察到滑膜中细胞增生和增殖以及滑膜增厚。主要发现是滑膜、关节软骨和后胫骨生长板中 TGF-β表达增加，Smad2/3 在后 TGF-β磷酸化后增加（ELISA 检测 TGF-β表达：4 周；P=0.009，95%CI[260.1-1340.0]）（p-Smad2/3 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]）。然而，SHAM 模型和 CAM 模型之间骨形态发生蛋白（BMP）-2 和 Smad1/5/8 水平没有差异。
本研究表明，胫骨前不稳定导致后胫骨和滑膜中 TGF 表达水平发生变化，这种反应可能与骨赘形成有关。
