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First published on September 12, 2005, doi:10.1177/0363546505278701
This version was published on December 1, 2005
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The American Journal of Sports Medicine 33:1816-1824 (2005)
© 2005 American Orthopaedic Society for Sports Medicine

The Effect of Relaxin Treatment on Skeletal Muscle Injuries

Shinichi Negishi, MD, Yong Li, MD, PhD, Arvydas Usas, MD, Freddie H. Fu, MD and Johnny Huard, PhD*

From the University of Pittsburgh and Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania

* Address correspondence to Johnny Huard, PhD, 3460 Fifth Avenue, Pittsburgh, PA 15213 (e-mail: jhuard+{at}pitt.edu).

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 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.

Key Words: muscle laceration • muscle healing • muscle regeneration • antifibrosis agents • relaxin




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