title: The effect of unloading on gene expression of healthy and injured rotator cuffs.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Washington University, 660 South Euclid Campus Box 8233, St Louis, Missouri 63110, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Killian
authors.forename: C T
authors.initials: CT
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Thomopoulos
authors.forename: N
authors.initials: N
authors.lastname: Charlton
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.forename: L M
authors.initials: LM
authors.lastname: Galatz
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D003714:Denervation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D009121:Muscle Denervation / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D059467:Transcriptome; D015854:Up-Regulation; D016474:Weight-Bearing
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018006:Myogenic Regulatory Factors; C503819:Scx protein, rat