title: Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice.
abstract: Fatty infiltration in muscle is often observed in patients with sizable rotator cuff tear (RCT) and is thought to be an irreversible event that significantly compromises muscle plasticity and contraction strength. These changes in the mechanical properties of the affected muscle render surgical repair of RCT highly formidable. Therefore, it is important to learn more about the pathology of fatty infiltration to prevent this undesired condition. In the present study, we aimed to generate a mouse model that can reliably recapitulate some of the important characteristics of muscular fatty infiltration after RCT in humans. We found that fatty infiltration can be efficiently induced by a combination of the following procedures: denervation of the suprascapular nerve, transection of the rotator cuff tendon, and resection of the humeral head. Using this model, we found that platelet-derived growth factor receptor-α (PDGFRα)-positive mesenchymal stem cells are induced after this intervention and that inhibition of PDGFR signaling by imatinib treatment can significantly suppress fatty infiltration. Taken together, the present study presents a reliable fatty infiltration mouse model and suggests a key role for PDGFRα-positive mesenchymal stem cells in the process of fatty infiltration after RCT in humans.
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shirasawa
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oki
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoda
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Tohmonda
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedic Surgery, and Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Horiuchi
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015415:Biomarkers; D003714:Denervation; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D000068877:Imatinib Mesylate / Q000494:pharmacology; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D000070636:Rotator Cuff Injuries / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D013710:Tendons / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor