The effect of relaxin treatment on skeletal muscle injuries

BACKGROUND: Injured skeletal muscle can repair itself via spontaneous regeneration; however, the overproduction of extracellular matrix and excessive collagen deposition lead to fibrosis. Neutralization of the effect of transforming growth factor-beta 1, a key fibrotic cytokine, on myogenic cell differentiation after muscle injury can prevent fibrosis, enhance muscle regeneration, and thereby improve the functional recovery of injured muscle. HYPOTHESIS: The hormone relaxin, a member of the family of insulin-like growth factors, can act as an antifibrosis agent and improve the healing of injured muscle. STUDY DESIGN: Controlled laboratory study. METHODS: In vitro: Myoblasts (C2C12 cells) and myofibroblasts (transforming growth factor-beta 1-transfected myoblasts) were incubated with relaxin, and cell growth and differentiation were examined. Myogenic and fibrotic protein expression was determined by Western blot analysis. In vivo: Relaxin was injected intramuscularly at different time points after laceration injury. Skeletal muscle healing was evaluated via histologic, immunohistochemical, and physiologic tests. RESULTS: Relaxin treatment resulted in a dose-dependent decrease in myofibroblast proliferation, down-regulated expression of the fibrotic protein alpha-smooth muscle actin, and promoted the proliferation and differentiation of myoblasts in vitro. Relaxin therapy enhanced muscle regeneration, reduced fibrosis, and improved injured muscle strength in vivo. CONCLUSION: Administration of relaxin can significantly improve skeletal muscle healing. CLINICAL RELEVANCE: These findings may facilitate the development of techniques to eliminate fibrosis, enhance muscle regeneration, and improve functional recovery after muscle injuries.