Fat accumulation, fibrosis, fiber‐type switching, and a reduction in specific force production following rotator cuff tear

Abstract

Rotator cuff tears often cause pain and decreased mobility, and are associated with atrophy of muscle fibers, fibrosis and accumulation of fat in the muscle, collectively referred to as “fatty atrophy.” Previous studies have demonstrated that surgical repair of torn cuff muscles does not reduce fatty atrophy. As the molecular etiology of fatty atrophy remains unknown, gaining greater insight into the mechanisms that lead to the development of fatty atrophy will improve the treatment of rotator cuff tears. Using a rat model, we measured single fiber contractility, fiber type distribution, and expression of various mRNA and miRNA transcripts involved in lipid accumulation and matrix synthesis in torn and intact cuff muscles. We hypothesized that following chronic rotator cuff tear, there would be a decrease in specific force, accumulation of type IIb fibers, and an upregulation of adipogenic and fibrogenic genes. Thirty days after inducing the tear, cuff muscles had a substantial decrease in mass and force production, a dramatic accumulation of type IIb fibers, and a marked increase in fatty macrophages and caspase positive fibers. While there was an increase in several mRNAs and miRNAs associated with fibrosis, only modest changes in canonical adipogenesis transcripts were observed. Combined, the fatty atrophy phenotype in torn rotator cuff muscles may be a result of autophagy rather than bona fide adipogenesis.