Effect of pERK2 on extracellular matrix turnover of the fibrotic joint capsule in a post-traumatic joint contracture model

Abstract

Abstract. Lentivirus (LV)-mediated extracellular signal-regulated kinase (ERK)2 small interfering RNA (siRNA) has previously been demonstrated to reduce post-traumatic joint contractures: In the present study, the effect of ERK2 siRNA on extracellular matrix turnover within fibrotic joint capsules in post-traumatic joint contractures was examined. Rats were randomly assigned to one of three groups as follows: The non-operated control (CON), operated contracture (ORC) and contracture-treatment (CNT) groups. Representative post-traumatic joint contracture was created through 8 weeks of immobilization following intra-articular injury. In the CNT group, LV-mediated ERK2 siRNA was injected into the model knee at days 3 and 7 after surgery. The posterior joint capsule was examined by western blotting, histology and immunohistochemistry to evaluate alterations in ERK2, phosphorylated (p)ERK2, total collagen, collagen I, collagen III, matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-13. In the ORC group, pERK2 was elevated and total collagen, collagen I, MMP-1 and MMP-13 were significantly increased (P<0.01 vs. CON group); however, these were significantly decreased in the CNT group, and pERK2 was downregulated (P<0.01 vs. ORC group). Collagen III and TIMP-13 were markedly decreased in the ORC group (P<0.01 vs. CON group), but elevated in the CNT group (P<0.01 vs. ORC group). The present res4ults demonstrate unique pathological changes of the fibrotic joint capsule that are responsible for joint contracture following traumatic injury, and reveal that extracellular matrix turnover can be affected by pERK2.

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

“…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. 17,18 Furthermore, Hagiwara et al 12 reported that the increased elasticity and structural changes of the posterior joint capsule may result in limited extension after a long period of immobilization in flexion. Most of studies involving joint contracture investigated the histological and molecular changes of joint contracture using the traumatic flexion joint contracture animal models, which involved two factors (including trauma and joint immobilization) that may influence the development of joint contracture.…”

Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro

“…Studies have shown that the TGF‐β1 signaling pathway mediated fibrosis in a variety of tissues . Additionally, we reported that TGF‐β1 stimulated fibroblast proliferation and tendon tissue adhesion . In this research, fibroblasts were exposed to HCPT, and the viability was reduced after treatment with TGF‐β1.…”

Metformin prevents peritendinous fibrosis by inhibiting transforming growth factor-β signaling

“…in vitro studies have also demonstrated that TGF-β1 strongly promoted cell proliferation and inhibited apoptosis [ 9 , 19 ]. Our previous studies have reported the activation of proliferation in TGF-β1-stimulated fibroblasts and adhesive tendon tissue [ 20 , 21 ]. However, TGF-β1-treated NIH/3T3 fibroblasts exposed to metformin showed decreased cell viability, and metformin treatment both promoted fibroblast apoptosis and inhibited proliferation.…”