BACKGROUND Current research lacks a model of knee extension contracture in rats.AIM To elucidate the formation process of knee extension contracture.METHODS We developed a rat model using an aluminum external fixator....BACKGROUND Current research lacks a model of knee extension contracture in rats.AIM To elucidate the formation process of knee extension contracture.METHODS We developed a rat model using an aluminum external fixator.Sixty male Sprague-Dawley rats with mature bones were divided into the control group(n=6)and groups that had the left knee immobilized with an aluminum external fixator for 1,2,and 3 d,and 1,2,3,4,6,and 8 wk(n=6 in each group).The passive extension range of motion,histology,and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization.After 2 wk,the contracture gradually changed from myogenic to arthrogenic.The arthrogenic contracture progressed slowly during the 1^(st) week,rapidly progressed until the 3^(rd) week,and then showed a steady progression until the 4^(rd) week.Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time.Correspondingly,the level of transforming growth factor beta 1(TGF-β1)and phosphorylated mothers against decapentaplegic homolog 2(p-Smad2)in the anterior joint capsule also increased with the immobilization time.Over time,the cross-sectional area of muscle fibers gradually decreased,while the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was increased.Unexpectedly,the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was decreased during the late stage of immobilization(6-8 wk).The myogenic contracture was stabilized after 2 wk of immobilization,whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.展开更多
The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy a...The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis.The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway,caspase system pathway,matrix metalloproteinase pathway,Ca2+-dependent pathway and autophagy-lysosomal pathway.The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α.This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments.Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.展开更多
基金Supported by Anhui Key Research and Development Program-Population Health,No.201904a07020067Anhui Provincial Health Research Project,No.AHWJ2022b063+2 种基金Clinical Medicine Discipline Construction Project of Anhui Medical University in 2022(Clinic and Preliminary Co-Construction Discipline Project),No.2022 lcxkEFY0102022 National Natural Science Foundation Incubation Plan,No.2022GMFY05Clinical Medicine Discipline Construction Project of Anhui Medical University in 2022(High-Level Personnel Training Program),No.2022 lcxkEFY04,No.2022 lcxkEFY05.
文摘BACKGROUND Current research lacks a model of knee extension contracture in rats.AIM To elucidate the formation process of knee extension contracture.METHODS We developed a rat model using an aluminum external fixator.Sixty male Sprague-Dawley rats with mature bones were divided into the control group(n=6)and groups that had the left knee immobilized with an aluminum external fixator for 1,2,and 3 d,and 1,2,3,4,6,and 8 wk(n=6 in each group).The passive extension range of motion,histology,and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization.After 2 wk,the contracture gradually changed from myogenic to arthrogenic.The arthrogenic contracture progressed slowly during the 1^(st) week,rapidly progressed until the 3^(rd) week,and then showed a steady progression until the 4^(rd) week.Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time.Correspondingly,the level of transforming growth factor beta 1(TGF-β1)and phosphorylated mothers against decapentaplegic homolog 2(p-Smad2)in the anterior joint capsule also increased with the immobilization time.Over time,the cross-sectional area of muscle fibers gradually decreased,while the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was increased.Unexpectedly,the amount of intermuscular collagen and TGF-β1,p-Smad2,and p-Smad3 was decreased during the late stage of immobilization(6-8 wk).The myogenic contracture was stabilized after 2 wk of immobilization,whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.
文摘The clinical treatment of joint contracture due to immobilization remains difficult.The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis.The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway,caspase system pathway,matrix metalloproteinase pathway,Ca2+-dependent pathway and autophagy-lysosomal pathway.The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α.This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments.Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
