title: Effect of pERK2 on extracellular matrix turnover of the fibrotic joint capsule in a post-traumatic joint contracture model.
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.
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Yangbai
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Fan
keywords: collagen; joint contracture; matrix metalloproteinase-1; matrix metalloproteinase-13; tissue inhibitor of metalloproteinase-13