Jonathan P Gumucio1, Michael A Korn1, Anjali L Saripalli2, Michael D Flood2, Anthony C Phan2, Stuart M Roche2, Evan B Lynch1, Dennis R Claflin3, Asheesh Bedi2, Christopher L Mendias4. 1. Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. 2. Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA. 3. Department of Biomedical Engineering, University of Michigan Medical School, Ann Arbor, MI, USA; Section of Plastic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA. 4. Department Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: cmendias@umich.edu.
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 messenger RNA and micro-RNA 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 after the 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. In addition, 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.
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 messenger RNA and micro-RNA 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 after the 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. In addition, 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.
Authors: Christopher L Mendias; Jonathan P Gumucio; Konstantin I Bakhurin; Evan B Lynch; Susan V Brooks Journal: J Orthop Res Date: 2011-09-12 Impact factor: 3.494
Authors: Christopher L Mendias; Evan B Lynch; Jonathan P Gumucio; Michael D Flood; Danielle S Rittman; Douglas W Van Pelt; Stuart M Roche; Carol S Davis Journal: J Physiol Date: 2015-02-25 Impact factor: 5.182
Authors: Benjamin B Rothrauff; Thierry Pauyo; Richard E Debski; Mark W Rodosky; Rocky S Tuan; Volker Musahl Journal: Tissue Eng Part B Rev Date: 2017-02-09 Impact factor: 6.389
Authors: Lauren K Wood; Erdan Kayupov; Jonathan P Gumucio; Christopher L Mendias; Dennis R Claflin; Susan V Brooks Journal: J Appl Physiol (1985) Date: 2014-07-03
Authors: Max E Davis; Michael A Korn; Jonathan P Gumucio; Julie A Harning; Anjali L Saripalli; Asheesh Bedi; Christopher L Mendias Journal: J Shoulder Elbow Surg Date: 2014-09-09 Impact factor: 3.019
Authors: Christopher L Mendias; Andrew J Schwartz; Jeremy A Grekin; Jonathan P Gumucio; Kristoffer B Sugg Journal: J Appl Physiol (1985) Date: 2016-12-15
Authors: Hugo Giambini; Taku Hatta; Krzysztof R Gorny; Per Widholm; Anette Karlsson; Olof D Leinhard; Mark C Adkins; Chunfeng Zhao; Kai-Nan An Journal: Muscle Nerve Date: 2017-05-15 Impact factor: 3.217