Muscle gene expression patterns in human rotator cuff pathology

Choo A, McCarthy M, Pichika R, Sato EJ, Lieber RL, Schenk S, Lane JG, Ward SR.
J Bone Joint Surg Am, 2014 96(18):1558-65.


BACKGROUND: Reconstruction of grasp is a high priority for tetraplegic patients. Restoration of finger flexion by surgical activation of flexor digitorum profundus can result in roll-up finger flexion, interphalangeal (IP) joint before metacarpophalangeal (MCP) joint flexion, which can be improved by restoring intrinsic function. This study compares grasp kinematics between 2 intrinsic balancing procedures-Zancolli-lasso and House.
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.
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.

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