title: Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator-cuff muscle.
abstract: The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)-based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alpha-bungarotoxin staining, and the γ:ε subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU+ (activated) Pax7+ satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher γ:ε subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome.
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Deanna
authors.initials: D
authors.lastname: Gigliotti
authors.affiliation: Pan Am Clinic, Winnipeg, Manitoba, Canada.
authors.forename: Jeff R S
authors.initials: JR
authors.lastname: Leiter
authors.affiliation: College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Bryce
authors.initials: B
authors.lastname: Macek
authors.affiliation: Department of Radiology, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davidson
authors.affiliation: Section of Orthopedics, Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; and.
authors.forename: Peter B
authors.initials: PB
authors.lastname: MacDonald
authors.affiliation: Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Judith.Anderson@umanitoba.ca.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000818:Animals; D057645:Deltoid Muscle / Q000294:innervation* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000473:pathology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D017006:Rotator Cuff / Q000294:innervation* / Q000473:pathology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology*; D012782:Shoulder / Q000294:innervation / Q000473:pathology
chemical_list: D009569:Nitric Oxide
keywords: Pax7; acetylcholine receptor; deltoid; nitric oxide; supraspinatus