Differential response to rotator cuff tear in C57BL/6J mice and MRL/MpJ mice
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PROVIDER: PRJNA540272 | ENA |
REPOSITORIES: ENA
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Project description:Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis.
2018-08-29 | GSE103266 | GEO
Project description:We harvested the blood samples from rotator cuff tear patients with and without shoulder stiffness.Then, circulating exosomes were harvested, and the miRNAs content was analyzed with an aim to idenfity differentially expressed miRNAs.
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Project description:We report RNA sequencing data from the infraspinatus muscles of 3-month old male C57BL/6J (Jackson Labs stock 000664) or MRL/MpJ mice (Jackson Labs stock 000486). Mice underwent a full-thickness infraspinatus tenectomy and denervation, and four weeks later muscles were collected for analysis. Comparisons are made to control male mice of the same strains who did not undergo infraspinatus tenectomy and denervation.
2019-09-26 | GSE130447 | GEO
Project description:In this study, we collected rabbit supraspinatus muscle tissue with higher temporal resolution (1, 2, 4, 8 weeks)after 8 wk tear followed by repair (n=4/group), to determine time-depenet transcriptional changes after repair. RNA sequencing and analyses were performed using standard techniques to identify a transcriptional timeline of rotator cuff muscle changes and related morphological sequelae.
2023-04-26 | GSE186320 | GEO
Project description:Myosteatosis, also known as fatty infiltration, is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following rotator cuff injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Identifying how reduced mechanical loading activates molecular pathways that lead to myosteatosis could help to develop targeted therapies to improve functional outcomes after rotator cuff repair. Our objective was to use cutting compare muscle fiber contracility, proteomic, RNA sequencing and shotgun metabolomics along with bioinformatics to identify potential pathways and cellular processes that are dysregulated after rotator cuff teaar.
2020-04-15 | PXD009034 | Pride
Project description:Rotator cuff tear is a common disease in elderly patients. The satellite cell has central role of muscle regeneration, however, there are few reports about human muscle. The purpose of this study was to compare features of human myogenic and adipogenic precursors in both torn supraspinatus (SSP) and intact subscapularis (SSC). Comprehensive gene expression patterns were compared between SSP and SSC muscles by microarray analisys.
2017-12-31 | GSE93661 | GEO
Project description:The samples consist of cells from two muscle types in mice – rotator cuff and gastrocnemius muscles. The aim of the project is to study the methylation differences between the two muscle types, specifically in genes involved in adipogenesis and muscle regeneration in the rotator cuff muscle with the gastrocnemius muscle being the control.
2018-09-29 | GSE112867 | GEO
Project description:In this study, we collected rabbit supraspinatus muscle tissue with higher temporal resolution (1, 2, 4, 8, 16 weeks) post-tenotomy (n=6/group), where muscle degeneration occurs at later time points, to determine if transcriptional changes occur. RNA sequencing and analyses were performed using standard techniques to identify a transcriptional timeline of rotator cuff muscle changes and related morphological sequelae.
2021-07-14 | GSE173234 | GEO
Project description:Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury.
2024-11-06 | PXD043481 | Pride
Project description:Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation, which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared with the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing and shotgun metabolomics and lipidomics were also performed. The muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. The markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:811-822, 2020.
| S-EPMC7071998 | biostudies-literature