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‘QuickDASH’ to find Unique Genes and Biological Processes Associated with Shoulder Osteoarthritis: a prospective case-control study

ABSTRACT: Osteoarthritis (OA) is a disease impacting the synovial joint complex, yet transcriptional changes specific to shoulder OA remain underexplored. This study aims to profile transcriptomic changes in periarticular tissues from patients undergoing shoulder replacement for OA. By correlating these profiles with QuickDASH scores—a validated measure of worsening shoulder function—this research seeks to understand the gene expression changes associated with clinical decline. Capsular tissue biopsies from shoulder OA patients were compared with those from a control group undergoing shoulder stabilization for recurrent instability. This investigation forms part of a larger transcriptomic analysis of painful shoulder conditions which will address the current gap in knowledge regarding the molecular and genetic underpinnings of shoulder OA, rotator cuff tears and cuff-tear arthropathy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281476 | GEO | 2024/12/03

REPOSITORIES: GEO

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Project description:Objective To identify transcript level differences between traumatic and degenerative tears of tendon tissues in shoulder joint using RNA-seq. Methods Tendon tissues were isolated from female and male patients with traumatic or degenerative tears during arthroscopic surgery (N = 31). Differentially expressed transcript were identified and biological processes enriched in traumatic and degenerative tears were probed computationally. Expression pattern of selected transcripts was validated by real-time qPCR. Results We identified 339 and 336 transcripts differentially expressed between traumatic and degenerative tears in females and males respectively at a fold-change greater than |2| and a p-value  0.05. In females, GSTM1, MT1G, S1008A, ACSM3, DSC, FAM110C and VNN2 were the most prominent transcripts elevated in traumatic tears and CHAD, CLEC3A, IBSP, TNMD, APLNR, and CPA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented catabolic processes, immune response, and metabolic processes while those repressed in traumatic tears represented tissue morphogenesis and developmental processes, angiogenesis, and extracellular matrix organization. In males, ELOA3B, CXCL8, ADM, TNS4 and SPOCK1 were the most prominent transcripts elevated in traumatic tears and MYL2, TNNC1, MB, CPA3, APLNR, and CA3 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented localization of endoplasmic reticulum, chromosome organization, leukocyte/neutrophil degranulation, and protein transport whereas those repressed in traumatic tears represented muscle development, blood circulation (angiogenesis), and muscle cell differentiation. Numerous novel lncRNAs were also identified to be differentially expressed between traumatic and degenerative tears in both sexes. Conclusions and Clinical Relevance This study improves our molecular understanding of tendon tissues in patients with rotator cuff tendinopathy based on underlying etiology (trauma and degeneration). It also provides new insights into sex-based transcript differences that may help drive clinical decision making in female and male patients with traumatic and degenerative shoulder injuries.

Project description:Objective: To identify transcript level differences between traumatic and degenerative tears of subacromial bursal tissues in shoulder joint using RNA-seq. Methods: Bursal tissues were collected from female and male patients with traumatic or degenerative tears during arthroscopic surgery (N=32). Differentially expressed transcript between traumatic and degenerative tears were detected by RNA-seq and biological processes were identified computationally. RNA-seq results were selectively validated by real-time qPCR. Results: We identified 334 protein-coding transcripts differentially expressed between traumatic and degenerative tears in females and 167 in males at a fold-change greater than |2| and a P < 0.05. In females, XIRP2, MYL1, MYBPC1, TNNT1, and LMOD2, were the highly expressed in traumatic tears and TPSD1, CDSN, RCVRN, LTBP4, and PTGS1 were prominently repressed in traumatic tears. Transcripts elevated in traumatic tears represented muscle cell differentiation and development, and muscle contraction whereas those elevated in degenerative tears represented cell activation, neutrophil granulation, immune response, and protein transport. In males, AZGP1, CNTFR, COL9A1, ZNF98 and EREG were highly elevated in traumatic tears whereas MYL2, HOXD11, SLC6A7, CADM1, and MMP17 were most highly repressed in traumatic tears. Transcripts elevated in traumatic tears represented metabolic processes, catabolic processes, and transmembrane protein transport while processes related to cell cycle were mainly repressed in traumatic tears. We also identified a number of novel lncRNAs differentially expressed between traumatic and degenerative tears in both females and males. Conclusions: This study increases our molecular understanding of bursal tissues in patients with rotator cuff tendinopathy based on the nature of disease that is trauma or degeneration. These finding also provide new insights into sex-based transcript differences that could inform clinical decision making in treating patients with traumatic and degenerative shoulder injuries.

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.

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‘QuickDASH’ to find Unique Genes and Biological Processes Associated with Shoulder Osteoarthritis: a prospective case-control study

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