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

Abstract

Background 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. Methods 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. Results 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. Conclusions Inhibiting TGF-β signaling paired with active motion effectively attenuated the formation of immobilization-induced joint contracture in rats.

Possible mechanism of static progressive stretching combined with extracorporeal shock wave therapy in reducing knee joint contracture in rats based on MAPK/ERK pathway

“…Joint contracture is a fibrotic disease characterized by limitation in range of motion (ROM) of the joint [1,2]. Once developed, the patients' quality of life is greatly affected, permanent contracture with continuous deterioration develops, and the patient becomes permanently disabled [1,3]. Among many causes of joint contracture, joint immobilization is the most common one [1][2][3][4].…”

“…Once developed, the patients' quality of life is greatly affected, permanent contracture with continuous deterioration develops, and the patient becomes permanently disabled [1,3]. Among many causes of joint contracture, joint immobilization is the most common one [1][2][3][4]. In the process of joint immobilization, arthrogenic and myogenic components are involved in the occurrence and development of joint contracture [1,3].…”

“…Among many causes of joint contracture, joint immobilization is the most common one [1][2][3][4]. In the process of joint immobilization, arthrogenic and myogenic components are involved in the occurrence and development of joint contracture [1,3]. The myogenic components mainly limit the ROM in short-term immobilization, which can return to the normal level after remobilization; the arthrogenic components play a dominant role in long-term immobilization, which cannot be effectively relieved even with a prolonged remobilization [5].…”