Background Rotator cuff tears are one of the most common musculoskeletal complaints and a substantial source of morbidity in elderly patients. Chronic cuff tears are associated with muscle atrophy and an infiltration of fat to the area, a condition known as “fatty degeneration.” To improve the treatment of cuff tears in elderly patients, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential. Methods Using a full-thickness, massive supraspinatus and infraspinatus tear model in elderly rats, we measured fiber contractility and determined changes in fiber type distribution that develop 30 days after tear. We also measured the expression of mRNA and miRNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of muscle fibers, an accumulation of type IIb fibers, and an upregulation in atrophic, fibrogenic, and inflammatory gene expression would occur in torn cuff muscles. Results Thirty days following tear, we observed a reduction in muscle fiber force and an induction of RNA molecules that regulate atrophy, fibrosis, lipid accumulation, inflammation and macrophage recruitment. A marked accumulation of advanced glycation end products, and a significant accretion of macrophages in areas of fat accumulation were observed. Conclusions The extent of degenerative changes in old rats was greater than that observed in adults. Additionally, we identified that the ectopic fat accumulation that occurs in chronic cuff tears does not occur by activation of canonical intramyocellular lipid storage and synthesis pathways.

The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, ECM production and angiogenesis that occur during muscle growth.

Background-Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation and fat accumulation. Identifying therapies to prevent the development of these pathologies will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated antiinflammatory and anti-fibrotic effects in many tissues, but had not previously been studied in the context of rotator cuff tears. We hypothesized that following the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis. Methods-We measured changes in muscle fiber contractility, histology and biochemical markers of fibrosis and fatty infiltration in rats that received a full-thickness supraspinatus tear and were treated with either carrier alone or simvastatin. Results-Compared to vehicle treated controls, simvastatin did not have an appreciable effect on muscle fiber size, but treatment did increase muscle fiber specific force by 20%. Simvastatin also reduced collagen accumulation by 50%, but did not effect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis and regeneration were also observed. Conclusions-Simvastatin partially protected muscles from the weakness that occurs as a result of chronic rotator cuff tear. Fibrosis was also markedly reduced in simvastatin treated animals. While further studies are necessary, statin medication could potentially help to improve outcomes for patients with rotator cuff tears.

Background Chronic rotator cuff tears are a common source of shoulder pain and disability, and patients with chronic cuff tears often have substantial weakness, fibrosis, inflammation and fat accumulation. Identifying therapies to prevent the development of these pathologies will likely have a positive impact on clinical outcomes. Simvastatin is a drug with demonstrated anti-inflammatory and anti-fibrotic effects in many tissues, but had not previously been studied in the context of rotator cuff tears. We hypothesized that following the induction of a massive supraspinatus tear, simvastatin would protect muscles from a loss of force production and fibrosis. Methods We measured changes in muscle fiber contractility, histology and biochemical markers of fibrosis and fatty infiltration in rats that received a full-thickness supraspinatus tear and were treated with either carrier alone or simvastatin. Results Compared to vehicle treated controls, simvastatin did not have an appreciable effect on muscle fiber size, but treatment did increase muscle fiber specific force by 20%. Simvastatin also reduced collagen accumulation by 50%, but did not effect triglyceride content of muscles. Several favorable changes in the expression of genes and other markers of inflammation, fibrosis and regeneration were also observed. Conclusions Simvastatin partially protected muscles from the weakness that occurs as a result of chronic rotator cuff tear. Fibrosis was also markedly reduced in simvastatin treated animals. While further studies are necessary, statin medication could potentially help to improve outcomes for patients with rotator cuff tears.

Chronic skeletal muscle injuries or tears can lead to the induction of myosteatosis, which is muscle atrophy combined with an accumulation of lipid plaques. Simvastatin is a drug that has demonstrated the ability to prevent lipid accumulation in other injured tissues. We hypothesized that administering simvastatin would reduce myosteatosis following muscle injuries. As the rotator cuff muscle group is especially prone to the development of myosteatosis, to test our hypothesis we performed a full‐thickness supraspinatus tenectomy and administered vehicle or simvastatin for 4 weeks. Compared to controls, simvastatin treatment increased muscle fiber specific force by 19% and decreased visible fat around fibers. Expression of several genes associated with fat accumulation, inflammation, macrophage accumulation, and extracellular matrix fibrosis was significantly decreased. Simvastatin also reduced the percent of pathological type IIB muscle fibers by 39%. These results suggest that simvastatin can protect muscles from the development of myosteatosis, and be useful in the clinical treatment of chronic muscle injuries and tears.