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Abstract
BackgroundRotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known.Methods and FindingsPotential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since “muscle” was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli.ConclusionsSince SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest indices including satellite cell responsiveness, atrogin-1, atrophy, and innervation may predict surgical outcome.
Highlights
The rotator cuff muscle complex of the shoulder is comprised of 4 distinct muscles and controls shoulder movements essential for performing normal activities of daily living such as eating, self-grooming, and lifting objects
Since supraspinatus muscle (SS) satellite cells can be activated in culture, a nitric oxide (NO)-donor drug combined with stretching could promote muscle growth and improve functional outcome after Rotator cuff injury (RCI)
Failure rate ranges from 30–94% [7], which is reported to relate to adverse changes in muscle, including fatty infiltration, fibrosis and/or denervation [8, 9]
Summary
The rotator cuff muscle complex of the shoulder is comprised of 4 distinct muscles (supraspinatus, infraspinatus, teres minor and subscapularis) and controls shoulder movements (internal and external rotation) essential for performing normal activities of daily living such as eating, self-grooming, and lifting objects. Rotator cuff injury (RCI) to the supraspinatus muscle (SS), causes intense shoulder pain and weakness [1] through tendon tear and/or impingement, suprascapular nerve injury [2, 3], and inflammation [3]. Damage can be chronic and agerelated, from repetitive strain or prolonged use, or acute and related to sudden, high-stress motion or impact [1, 4,5,6]. It is not understood why surgical repair of the SS tendon after RCI frequently fails to restore full joint function and stability. Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known
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