title: Selective Retinoic Acid Receptor γ Agonists Promote Repair of Injured Skeletal Muscle in Mouse.
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.
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia Research Institute, Philadelphia.
authors.forename: Agnese
authors.initials: A
authors.lastname: Di Rocco
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia Research Institute, Philadelphia.
authors.forename: Kenta
authors.initials: K
authors.lastname: Uchibe
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia Research Institute, Philadelphia.
authors.forename: Colleen
authors.initials: C
authors.lastname: Larmour
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia Research Institute, Philadelphia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Berger
authors.affiliation: Department of Physiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, The Children's Hospital of Philadelphia Research Institute, Philadelphia. Electronic address: iwamotom@email.chop.edu.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
mesh_terms: D000818:Animals; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D000097768:Retinoic Acid Receptor gamma
chemical_list: D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma