title: Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear.
abstract: BACKGROUND
  Rotator cuff tears are one of the most common musculoskeletal complaints and a substantial source of morbidity in elderly patients. Chronic cuff tears are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of cuff tears in elderly patients, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential.
  
  
  METHODS
  Using a full-thickness, massive supraspinatus and infraspinatus tear model in elderly rats, we measured fiber contractility and determined changes in fiber type distribution that develop 30 days after tear. We also measured the expression of messenger RNA and micro-RNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of muscle fibers, an accumulation of type IIb fibers, and an upregulation in atrophic, fibrogenic, and inflammatory gene expression would occur in torn cuff muscles.
  
  
  RESULTS
  Thirty days after the tear, we observed a reduction in muscle fiber force and an induction of RNA molecules that regulate atrophy, fibrosis, lipid accumulation, inflammation, and macrophage recruitment. A marked accumulation of advanced glycation end products and a significant accretion of macrophages in areas of fat accumulation were observed.
  
  
  CONCLUSIONS
  The extent of degenerative changes in old rats was greater than that observed in adults. In addition, we identified that the ectopic fat accumulation that occurs in chronic cuff tears does not occur by activation of canonical intramyocellular lipid storage and synthesis pathways.
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Korn
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Anjali L
authors.initials: AL
authors.lastname: Saripalli
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Flood
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Phan
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Roche
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Evan B
authors.initials: EB
authors.lastname: Lynch
authors.affiliation: Department of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, MI, USA; Section of Plastic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Claflin
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Asheesh
authors.initials: A
authors.lastname: Bedi
authors.affiliation: Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: cmendias@umich.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000378:metabolism* / Q000473:pathology; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Animal Model; Basic Science Study; Fatty degeneration; Molecular and Cell Biology; atrophy; lipid droplets; macrophages; rotator cuff; sarcopenia