Muscle gene expression patterns in human rotator cuff pathology

Alexander Choo*, Meagan McCarthy, Rajeswari Pichika, Eugene J. Sato, Richard L. Lieber, Simon Schenk, John G. Lane, Samuel R. Ward

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

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.

Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that themuscle was not in a state of active change andmay have difficulty responding to stimuli. Patients with a fullthickness 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.

Clinical Relevance: 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.

Original languageEnglish (US)
Pages (from-to)1558-1565
Number of pages8
JournalJournal of Bone and Joint Surgery - American Volume
Volume96
Issue number18
DOIs
StatePublished - Sep 17 2014

Funding

Financial support for this work was provided by the Orthopaedic Research and Education Foundation and NIH (National Institutes of Health) grants R24 HD050837 and R01 HD073180.

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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