Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

Abstract

The purpose of this study was to examine the time-dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule after immobilization, using a rat knee contracture model. Both knee joints were fixed in full flexion for 1, 2, and 4 weeks (immobilization group). Untreated rats were bred for each immobilization period (control group). Histological analysis was performed to evaluate changes in the amount and density of collagen in the joint capsule. The changes in type I and III collagen mRNA were examined by in situ hybridization. The number of myofibroblasts in the joint capsule was assessed by immunohistochemical methods. In the immobilization group, the amount of collagen increased within 1 week and the density of collagen increased within 2 weeks, as compared with that in the control group. Type I collagen mRNA-positive cell numbers in the immobilization group increased at all time points. However, type III collagen mRNA-positive cell numbers did not increase. Myofibroblasts in the immobilization group significantly increased compared with those in the control group at all time points, and they increased significantly with the period of immobilization. These results suggest that joint capsule fibrosis with overexpression of type I collagen occurs and progresses within 1 week after immobilization, and an increase in myofibroblasts is related to the mechanism of joint capsule fibrosis. The findings suggest the need for a treatment targeting accumulation of type I collagen associated with an increase in myofibroblasts. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1998-2006, 2017.

Rabbit Model of Extending Knee Joint Contracture: Progression of Joint Motion Restriction and Subsequent Joint Capsule Changes after Immobilization

“…capsule, and synovial membrane, while the myogenic components are lesions of the muscle, tendon, and fascia. 6,12 Arthrogenic components, particularly regarding the joint capsule, are reportedly important factors in the formation of immobilization-induced joint contracture. 6,13,14 Reported changes in the capsule after immobilization include proliferation of connective tissues within the joint space, and adhesions in the capsule and synovial membrane.…”

“…6,12 Arthrogenic components, particularly regarding the joint capsule, are reportedly important factors in the formation of immobilization-induced joint contracture. 6,13,14 Reported changes in the capsule after immobilization include proliferation of connective tissues within the joint space, and adhesions in the capsule and synovial membrane. 15,16 Some studies reported that joint capsule fibrosis may occur in the posttraumatic joint contracture caused by joint immobilization in flexion in rabbit or rat models.…”

“…Nevertheless, some studies showed that patients with conditions limiting their mobility but without traumatic or inflammatory conditions are also at a high risk for joint contracture. 6,13,19 During the process of joint contracture formation, the expressions of many growth factors, cytokines, and matrix metalloproteinases may be changed, which can contribute to joint contracture. 20,21 Hildebrand et al 22 reported elevated expressions of collagen types I and III and transforming growth factor β1 (TGF-β1) in the experimental posterior joint capsules compared with control capsules in a rabbit posttraumatic contracture model.…”

Intra-Articular Injection of Mitomycin C Prevents Progression of Immobilization-Induced Arthrogenic Contracture in the Remobilized Rat Knee

“…Fibrosis in the joint components is believed to be the major factor contributing to development of arthrogenic contracture in injured (Fukui et al 2000, Fukui et al 2001, Gao et al 2017, Li et al 2013a and immobilized joints (Sasabe et al 2017). For example, administration of decorin, which suppresses bioactivity of cell adhesion, as well as fibrotic regulators, such as transforming growth factor-beta, can improve restricted joint motion in the rabbit intra-articular adhesion model (Fukui et al 2001).…”

The mechanisms and treatments of muscular pathological changes in immobilization-induced joint contracture: A literature review

“…5 In addition to this, there are differences in the rate of progression of joint contracture caused by immobilization between different species. 6 , 7 Despite this, joint function can be restored by removing joint immobilization and reactivating. For example, flexing knee joint contracture that occurs in rats in 2 weeks can be completely restored, but it is difficult to restore completely when immobilization time over 4 weeks.…”