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

First Author  Di Rocco A Year  2015
Journal  Am J Pathol Volume  185
Issue  9 Pages  2495-504
PubMed ID  26205250 Mgi Jnum  J:226042
Mgi Id  MGI:5695697 Doi  10.1016/j.ajpath.2015.05.007
Citation  Di Rocco A, et al. (2015) Selective Retinoic Acid Receptor gamma Agonists Promote Repair of Injured Skeletal Muscle in Mouse. Am J Pathol 185(9):2495-504
abstractText  Retinoic acid signaling regulates several biological events, including myogenesis. We previously found that retinoic acid receptor gamma (RARgamma) agonist blocks heterotopic ossification, a pathological bone formation that mostly occurs in the skeletal muscle. Interestingly, RARgamma agonist also weakened deterioration of muscle architecture adjacent to the heterotopic ossification lesion, suggesting that RARgamma 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 RARgamma agonist or vehicle corn oil, and examined the effects of RARgamma 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 RARgamma-treated and control groups. The fibrous or adipose area was smaller in RARgamma agonist-treated mice than in the control. In addition, muscle repair was remarkably delayed in RARgamma-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 RARgamma signaling is involved in muscle repair and that selective RARgamma agonists may be beneficial to promote repair in various types of muscle injuries.
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