Joint immobilization is frequently administered after fractures and ligament injuries and can cause joint contracture as a side effect. The structures responsible for immobilization-induced joint contracture can be roughly divided into muscular and articular. During remobilization, although myogenic contracture recovers spontaneously, arthrogenic contracture is irreversible or deteriorates further. Immediately after remobilization, an inflammatory response is observed, characterized by joint swelling, deposit formation in the joint space, edema, inflammatory cell infiltration, and the upregulation of genes encoding proinflammatory cytokines in the joint capsule. Subsequently, fibrosis in the joint capsule develops, in parallel with progressing arthrogenic contracture. The triggers of remobilization-induced joint inflammation are not fully understood, but two potential mechanisms are proposed: 1) micro-damage induced by mechanical stress in the joint capsule, and 2) nitric oxide (NO) production via NO synthase 2. Some interventions can modulate remobilization-induced inflammatory and subsequent fibrotic reactions. Anti-inflammatory treatments, such as steroidal anti-inflammatory drugs and low-level laser therapy, can attenuate joint capsule fibrosis and the progression of arthrogenic contracture in remobilized joints. Antiproliferative treatment using the cell-proliferation inhibitor mitomycin C can also attenuate joint capsule fibrosis by inhibiting fibroblast proliferation without suppressing inflammation. Conversely, aggressive exercise during the early remobilization phases is counterproductive, because it facilitates inflammatory and then fibrotic reactions in the joint. However, the adverse effects of aggressive exercise on remobilization-induced inflammation and fibrosis are offset by anti-inflammatory treatment. To prevent the progression of arthrogenic contracture during remobilization, therefore, care should be taken to control inflammatory and fibrotic reactions in the joints.

• MeSH
• antiflogistika farmakologie   MeSH
• fibróza MeSH
• kolenní kloub MeSH
• kontraktura * farmakoterapie   MeSH
• lidé MeSH
• rozsah kloubních pohybů MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika MeSH

This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.

• MeSH
• fibroblasty účinky léků   MeSH
• imobilizace škodlivé účinky   MeSH
• injekce intraartikulární MeSH
• kloubní pouzdro účinky léků   MeSH
• kontraktura farmakoterapie   etiologie   MeSH
• mitomycin aplikace a dávkování   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• proliferace buněk účinky léků   MeSH
• protinádorová antibiotika aplikace a dávkování   MeSH
• rozsah kloubních pohybů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mitomycin MeSH
• protinádorová antibiotika MeSH