Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear

Abstract

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.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears

“…6,16,17,21 Briefly, bundles of muscle fibers approximately 5 mm in length and 0.5 mm in diameter were dissected from supraspinatus muscle biopsy specimens and exposed to skinning solution for 30 minutes. Bundles were then transferred to storage solution for 16 hours at 4 C and then stored at À80 C until use.…”

“…6 Histology Histology was performed as previously described. 16,17 Biopsied tissue was rinsed free of blood with saline and was snap frozen in Tissue-Tek (Sakura, Torrance, CA, USA) with isopentane cooled in liquid nitrogen and stored at À80 C until use. Muscles were sectioned at a thickness of 10 mm and prepared for immunohistochemistry.…”

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

“…Muscle atrophy and fatty infiltration are major deleterious phenomena in RCT and are closely correlated with poor functional outcome following even adequate repair because they have been considered irreversible phenomena 1, 6, 7. Therefore, RCT could be considered a good model to understand age‐associated muscle fatty infiltration.…”

Muscle Fibers are Injured at the Time of Acute and Chronic Rotator Cuff Repair

“…Owing to the presence of EBD in muscles, we did not directly measure gene expression or biochemical markers of atrophy or inflammation, because the presence of this dye makes many biochemical measures difficult. However, there already is a large body of work that has evaluated these markers at similar times [12,13,18,24]. We also did not directly measure tendon retraction, although we did take care to ensure the tendon was secured in silicone and at the time of harvest verified the tendon encased in silicone was free of lateral adhesions to surrounding connective tissue.…”

“…1). The surgical procedure was described in previous studies [12,13,17]. In brief, rats were anesthetized with 2% isoflurane and the skin above the shoulder was shaved and scrubbed with chlorhexidine/isopropanol.…”