title: Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after injury.
abstract: BACKGROUND
  rotator cuff muscle atrophy, fibrosis and fatty infiltration are common complications after large and massive rotator cuff tears. Currently, there are no effective treatments for these muscle pathologies after injury. Furthermore, the cellular source for fibrotic and adipose tissues in rotator cuff muscle after injury remains unknown. In this study, we proposed that two groups of muscle resident progenitors, Tie2+ muscle mesenchymal progenitors and PDGFRα(+) fibro/adipogenic progenitor cells (FAPs), contribute significantly to rotator cuff muscle fibrosis and fatty infiltration.
  
  
  METHODS
  we tested our hypothesis using reporter mice. Rotator cuff muscles from Tie2-GFP and PDGFRα-GFP reporter mice were harvested at 2 and 6 weeks after unilateral massive rotator cuff tear surgeries. Immunofluorescent staining for fibroblast and adipocyte markers was conducted.
  
  
  RESULTS
  our results showed significant co-localization of Tie2+ cells with fibrotic markers vimentin and αSMA. In the PDGFRα-GFP reporter mice, GFP signal was seen in only a small fraction of cells staining positive for vimentin and αSMA. However, PDGFRα showed significant co-localization with adipocyte markers, including PPAR-γ, adiponectin, and perilipin A. Oil red O staining confirmed that the mature adipocytes appearing in rotator cuff muscles after injury are also PDGFRα(+).
  
  
  CONCLUSIONS
  these data demonstrated that the Tie2(+) muscle mesenchymal progenitors are the major source of fibroblasts while PDGFRα(+) FAPs are the major source of adipocytes in rotator cuff muscle fatty infiltration. Basic Science Study.
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Anne Y
authors.initials: AY
authors.lastname: Ning
authors.affiliation: San Francisco Veterans Affairs Medical Center, USA.
authors.forename: Nai Chen
authors.initials: NC
authors.lastname: Chang
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Nissenson
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Feeley
keywords: Tie2; fatty infiltration; fibro-adipogenic progenitors; fibrosis; muscle; rotator cuff tear