The effect of relaxin treatment on skeletal muscle injuries.

Abstract

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.

• Authors: Shinichi Negishi, Yong Li, Arvydas Usas, Freddie H Fu, Johnny Huard
• Journal: The American journal of sports medicine (Am J Sports Med) Vol. 33 Issue 12 Pg. 1816-24 (Dec 2005) ISSN: 0363-5465 [Print] United States
• PMID: 16157846 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Desmin
• Myogenic Regulatory Factor 5
• Vimentin
• Relaxin
• Collagen

Topics

• Actins (metabolism)
• Animals
• Blotting, Western
• Cell Differentiation
• Cell Proliferation
• Collagen (metabolism)
• Desmin (metabolism)
• Down-Regulation
• Female
• Fibroblasts (metabolism)
• Fibrosis
• In Vitro Techniques
• Injections, Intramuscular
• Mice
• Muscle Fibers, Skeletal (metabolism)
• Muscle, Skeletal (injuries, pathology, physiology)
• Muscle, Smooth (metabolism)
• Myoblasts, Skeletal (metabolism)
• Myogenic Regulatory Factor 5 (metabolism)
• Regeneration
• Relaxin (pharmacology)
• Up-Regulation
• Vimentin (metabolism)
• Wound Healing (drug effects)