Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice

Hideyuki Shirasawa, Noboru Matsumura, Masayuki Shimoda, Satoshi Oki, Masaki Yoda, Takahide Tohmonda, Yae Kanai, Morio Matsumoto, Masaya Nakamura, Keisuke Horiuchi

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Article number41552
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017 Jan 31

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Platelet-Derived Growth Factor Receptors
Mesenchymal Stromal Cells
Humeral Head
Muscles
Rotator Cuff
Denervation
Muscle Contraction
Tendons
Pathology
Rotator Cuff Injuries
Therapeutics

ASJC Scopus subject areas

  • General

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Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice. / Shirasawa, Hideyuki; Matsumura, Noboru; Shimoda, Masayuki; Oki, Satoshi; Yoda, Masaki; Tohmonda, Takahide; Kanai, Yae; Matsumoto, Morio; Nakamura, Masaya; Horiuchi, Keisuke.

In: Scientific Reports, Vol. 7, 41552, 31.01.2017.

Research output: Contribution to journalArticle

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AU - Yoda, Masaki

AU - Tohmonda, Takahide

AU - Kanai, Yae

AU - Matsumoto, Morio

AU - Nakamura, Masaya

AU - Horiuchi, Keisuke

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