Rotator cuff injury is a debilitating condition and when injury cannot be managed through non-operative procedures, surgery is required. To determine explanations for the failure of surgery to restore joint function, human muscle biopsies of supraspinatus were studied compared to deltoid. Histology showed atrophy and a tendency toward fibrosis/fatty infiltration in injured supraspinatus. Findings from AChR-subunit western blot and Sema3A localization around satellite cells suggest supraspinatus denervation. Nucleotide incorporation to quantify satellite cell activation in culture showed a significant increase in BrdU+(active) satellite cells in supraspinatus treated with a nitric oxide-donor drug, but not deltoid muscle. The application of principal component analysis to these data extracted components that suggest variables assaying muscle atrophy, satellite cell activity, and fibrosis contribute strongly to the observed variability. The results suggest supraspinatus muscle of the injured rotator cuff is atrophic, denervated, possibly subject to fibro-fatty infiltration, and support the idea that treatment could promote growth in atrophic supraspinatus to improve functional outcomes. / October 2015