• Injury · Mar 2021

    Suppression of TGF-beta activity with remobilization attenuates immobilization-induced joint contracture in rats.

    • Dong Mao, Jingyi Mi, Xiaoyun Pan, Fengfeng Li, and Yongjun Rui.
    • Orthopaedic Institute, Wuxi 9th People's Hospital Affiliated to Soochow University, Wuxi, 214062, China.
    • Injury. 2021 Mar 1; 52 (3): 434-442.

    BackgroundJoint 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.MethodsThe 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.ResultsTGF-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.ConclusionsInhibiting TGF-β signaling paired with active motion effectively attenuated the formation of immobilization-induced joint contracture in rats.Copyright © 2020. Published by Elsevier Ltd.

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