Shinichi Negishi, MD, Yong Li, MD, PhD, Arvydas Usas, MD, Freddie H. Fu, MD and Johnny Huard, PhD*
From the University of Pittsburgh and Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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-ß 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-ß 1transfected 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 -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.
The American Journal of Sports Medicine 33:1816-1824 (2005).