Orthopaedic Institute, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, 214062, China.
Department of Sports Medicine, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, 214062, China.
Injury. 2021 Mar;52(3):434-442. doi: 10.1016/j.injury.2020.12.029. Epub 2020 Dec 31.
Joint contracture is a common complication of joint injury. This study aimed to assess the effect of inhibiting the transforming growth factor-β (TGF-β) signaling during joint immobilization and remobilization on immobilization-induced joint contracture in rats.
The knees of rats were immobilized using Kirschner wires following trauma to the femoral condyles to generate joint contracture. After immobilization, levels of TGF-β and passive extension range of motion (ROM) were measured at different time points, joints were histologically analyzed by hematoxylin and eosin (H&E) and Masson trichrome staining, and the expression of inflammatory or fibrosis-related mediators, including interleukin-1β (IL-1β), phosphorylated Smad2/3 (p-Smad2/3), α-smooth muscle actin (α-SMA) and collagen types I (Col 1) and III (Col 3), were examined in joint capsules using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Rats were also treated with LY2157299, a TGF-β receptor I kinase inhibitor, at different stages of immobilization and remobilization.
TGF-β1 levels in the serum and the number of p-Smad2/3 cells in the joint capsule were significantly elevated after immobilization. ROM decreased during the 6 weeks of immobilization and partly recovered after remobilization. After treatment with LY2157299 during immobilization, the restricted ROM moderately increased, but this effect was stronger when combined with active motion. Mechanistically, the expression of IL-1β, TGF-β, fibrosis-related factors, and the density of collagen significantly decreased after treatment with LY2157299.
Inhibiting TGF-β signaling paired with active motion effectively attenuated the formation of immobilization-induced joint contracture in rats.
关节挛缩是关节损伤的常见并发症。本研究旨在评估在关节固定和再活动期间抑制转化生长因子-β（TGF-β）信号对大鼠关节固定引起的关节挛缩的影响。
通过在股骨髁部创伤后使用克氏针固定膝关节，以产生关节挛缩。固定后，在不同时间点测量 TGF-β水平和被动伸展活动范围（ROM），通过苏木精和伊红（H&E）和 Masson 三色染色对关节进行组织学分析，并使用免疫组织化学和定量实时聚合酶链反应（qRT-PCR）检查关节囊中的炎症或纤维化相关介质，包括白细胞介素-1β（IL-1β）、磷酸化 Smad2/3（p-Smad2/3）、α-平滑肌肌动蛋白（α-SMA）和胶原类型 I（Col 1）和 III（Col 3）的表达。在固定和再活动的不同阶段，大鼠还接受 TGF-β受体 I 激酶抑制剂 LY2157299 的治疗。
固定后血清中 TGF-β1 水平和关节囊中 p-Smad2/3 细胞数量明显升高。ROM 在 6 周的固定期间减少，在再活动后部分恢复。在固定期间用 LY2157299 治疗后，受限 ROM 适度增加，但与主动运动结合时效果更强。从机制上讲，用 LY2157299 治疗后，IL-1β、TGF-β、纤维化相关因子和胶原密度的表达明显降低。
抑制 TGF-β信号与主动运动相结合可有效减轻大鼠关节固定引起的关节挛缩形成。
