The effect of unloading on gene expression of healthy and injured rotator cuffs

M. L. Killian, C. T. Lim, S. Thomopoulos, N. Charlton, H. M. Kim, L. M. Galatz

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Tendon unloading following rupture of one of the rotator cuff tendons can induce alterations in muscle physiology and tendon structure, which can subsequently affect reparability and healing potential. Yet little is known about the effects of muscle and tendon unloading on the molecular response of the rotator cuff. We determined the effect of mechanical unloading on gene expression and morphology of healthy supraspinatus tendons and muscles, and the same muscles after acute injury and repair. Mechanical unloading was achieved by tenotomy and/or botulinum toxin A (BTX) chemical denervation in a rat rotator cuff model of injury and repair. Gene expression profiles varied across regions of the muscle, with the greatest changes seen in the distal aspect of the muscle for most genes. Myogenic and adipogenic genes were upregulated in muscle when unloaded (tenotomy and BTX). Tendon injury, with and without repair, resulted in upregulation of fibrosis- and tendon-specific gene expression. The expression of scleraxis, a transcription factor necessary for tendon development, was upregulated in response to injury and repair. In summary, tendon detachment and repair had the greatest effect on tendon gene expression, while unloading had the greatest effect on muscle gene expression.

Original languageEnglish (US)
Pages (from-to)1240-1248
Number of pages9
JournalJournal of Orthopaedic Research
Issue number8
StatePublished - Aug 2013

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine


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