Selective Retinoic Acid Receptor γ Agonists Promote Repair of Injured Skeletal Muscle in Mouse

Agnese Di Rocco, Kenta Uchibe, Colleen Larmour, Rebecca Berger, Min Liu, Elisabeth R. Barton, Masahiro Iwamoto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Retinoic acid signaling regulates several biological events, including myogenesis. We previously found that retinoic acid receptor γ (RARγ) agonist blocks heterotopic ossification, a pathological bone formation that mostly occurs in the skeletal muscle. Interestingly, RARγ agonist also weakened deterioration of muscle architecture adjacent to the heterotopic ossification lesion, suggesting that RARγ agonist may oppose skeletal muscle damage. To test this hypothesis, we generated a critical defect in the tibialis anterior muscle of 7-week-old mice with a cautery, treated them with RARγ agonist or vehicle corn oil, and examined the effects of RARγ agonist on muscle repair. The muscle defects were partially repaired with newly regenerating muscle cells, but also filled with adipose and fibrous scar tissue in both RARγ-treated and control groups. The fibrous or adipose area was smaller in RARγ agonist-treated mice than in the control. In addition, muscle repair was remarkably delayed in RARγ-null mice in both critical defect and cardiotoxin injury models. Furthermore, we found a rapid increase in retinoid signaling in lacerated muscle, as monitored by retinoid signaling reporter mice. Together, our results indicate that endogenous RARγ signaling is involved in muscle repair and that selective RARγ agonists may be beneficial to promote repair in various types of muscle injuries.

Original languageEnglish
Pages (from-to)2495-2504
Number of pages10
JournalAmerican Journal of Pathology
Volume185
Issue number9
DOIs
Publication statusPublished - Sep 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Di Rocco, A., Uchibe, K., Larmour, C., Berger, R., Liu, M., Barton, E. R., & Iwamoto, M. (2015). Selective Retinoic Acid Receptor γ Agonists Promote Repair of Injured Skeletal Muscle in Mouse. American Journal of Pathology, 185(9), 2495-2504. https://doi.org/10.1016/j.ajpath.2015.05.007