title: Muscle gene expression patterns in human rotator cuff pathology.
abstract: BACKGROUND
  Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology.
  
  
  METHODS
  Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis.
  
  
  RESULTS
  Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear.
  
  
  CONCLUSIONS
  Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis.
  
  
  CONCLUSIONS
  These data highlight the difficulty in treating massive tears and suggest that the timing of treatment may be important for muscle recovery. Specifically, earlier interventions to address tendon injury may allow muscles to respond more appropriately to mechanical stimuli.
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Choo
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Meagan
authors.initials: M
authors.lastname: McCarthy
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Pichika
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Sato
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Simon
authors.initials: S
authors.lastname: Schenk
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Lane
authors.affiliation: Departments of Orthopaedic Surgery (A.C., M.M., R.P., S.S., and J.G.L.), Bioengineering (E.J.S. and R.L.L.), and Radiology (S.R.W.), University of California San Diego, 9500 Gilman Drive (0610), La Jolla, CA 92093. E-mail address for S.R. Ward: srward@ucsd.edu.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Ward
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue; D015536:Down-Regulation; D005260:Female; D005355:Fibrosis / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D005796:Genes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology; D009133:Muscular Atrophy / Q000235:genetics; D016133:Polymerase Chain Reaction; D000070636:Rotator Cuff Injuries; D012421:Rupture / Q000235:genetics; D020069:Shoulder Pain / Q000235:genetics; D052256:Tendinopathy / Q000235:genetics; D013708:Tendon Injuries / Q000235:genetics*