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.
Project description:Rotator cuff tear is frequently accompanied by progressive supraspinatus muscle degeneration, including muscle atrophy, fibrosis, fatty infiltration and inflammatory remodeling. In this study, we performed bulk RNA sequencing to investigate the transcriptional effects of a tissue-adaptive flexible ultrasound patch (TA-FUP) on supraspinatus muscle degeneration after rotator cuff injury. A rat rotator cuff injury model was established by supraspinatus tenotomy combined with suprascapular neurotomy. Injured animals were assigned to untreated control or TA-FUP treatment groups. During treatment, the muscle-side region of TA-FUP was positioned over the supraspinatus muscle and operated at 100 mW/cm², while the tendon-side region was positioned over the tendon-to-bone interface and operated at 50 mW/cm². TA-FUP treatment was administered three times per week for 10 min per session. Bulk RNA-seq was performed on supraspinatus muscle tissues from control and TA-FUP-treated rats to characterize treatment-induced transcriptional changes. Differential expression and pathway analyses showed that TA-FUP broadly reprogrammed the degenerative transcriptomic profile of injured supraspinatus muscle. Genes and pathways associated with adipogenesis, lipid transport, lipid metabolic process, extracellular matrix organization, collagen fibril organization, immune response and inflammatory response were downregulated after TA-FUP treatment. Gene set enrichment analysis further suggested enhanced fatty acid degradation and suppression of adipocyte-associated lipid remodeling, ECM-receptor interaction and NF-κB signaling. These data provide transcriptomic evidence that TA-FUP attenuates supraspinatus muscle degeneration after rotator cuff injury by suppressing adipogenic, fibrotic and inflammatory remodeling programs.
Project description:Rats were subjected to bilateral rotator cuff tears of the right and left supraspinatus muscle. Muscles were harvested from each shoulder at 0, 10, 30, or 60 days post surgery.
Project description:The purpose of this study is to identify dysregulated ncRNAs and understand how they influence Rotator cuff tears (RCT). We performed RNA sequencing and miRNA sequencing on 5 pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. Based on the results of differential expression analysis and miRNA targeting information, we constructed lncRNA/circRNA-associated dysregulated ceRNA networks in RCT. We found the largest module in the ceRNA network and identified several important ncRNAs in this module, which may have critical roles in RCT.
Project description:The purpose of this study is to identify dysregulated ncRNAs and understand how they influence Rotator cuff tears (RCT). We performed RNA sequencing and miRNA sequencing on 5 pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. Based on the results of differential expression analysis and miRNA targeting information, we constructed lncRNA/circRNA-associated dysregulated ceRNA networks in RCT. We found the largest module in the ceRNA network and identified several important ncRNAs in this module, which may have critical roles in RCT.
Project description:Rotator cuff tears are the most common upper extremity orthopaedic injury, causing degenerative changes within the bone, tendon, joint capsule, bursa, and muscle. These degenerative changes are linked to poor rehabilitative and surgical outcomes, which has launched investigations into co-therapeutic biologics. Specifically, Mesenchymal Stem Cells (MSCs) have shown promise in mitigating degenerative changes in animal models of RC tears, however reports of their impact on clinical outcomes remain mixed. Here we describe an alternative source of MSCs in the human shoulder, adipose stromal cells (ASCs) from the subacromial fat (SAF) pad. Compared to the gold-standard subcutaneous (SQ) fat, we show that SAF ASCs are less sensitive to chemical and mechanical fibrotic cues, 1) retaining smaller cell area with reduced actin stress fiber alignment across a range of physiological and pathological stiffnesses, 2) reduced traction forces and ECM production and 3) reduced myofibroblastic conversion in response to cytokine challenge. Furthermore, we show that SAF ASCs enhance fusion of primary human myoblasts via paracrine signaling. Despite a fibrotic signature in SAF from rotator cuffs with tendon tears, SAF ASCs sourced from torn rotator cuffs were equally effective at resisting fibroblastic conversion and promoting myogenesis as those from intact rotator cuffs, further supporting autologous clinical use of these cells. In conclusion, this study describes human SAF ASCs as an alternative, and potentially superior, cell source for rotator cuff therapies.
Project description:Rotator cuff tears are one of the most common shoulder disorders and can lead to pain, weakness, and limited mobility. Although the clinical condition has been widely studied, its molecular mechanisms are still not fully understood. In this study, we analyzed the proteomic profile of synovial fluid in patients with full-thickness rotator cuff tears and compared the results to those from a control group. Proteomic analysis was performed on synovial fluid samples from seven patients with full-thickness tears and three patients with partial-thickness tears, who served as the control group. Label-free quantification using the MaxQuant platform identified 284 proteins at 1% FDR. Among them, CLEC3B (tetranectin) showed the most significant difference, with a fold change of approximately 40 and a p-value of 2.6 × 10⁻³. Gene ontology enrichment analysis revealed biological processes related to extracellular matrix remodeling, fibrinolysis, and inflammation. Given its known roles in extracellular matrix remodeling, tetranectin identified as a candidate for full-thickness rotator cuff tears, providing insight into pathological processes such as tendon degeneration and fatty infiltration.
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.
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.
Project description:Rotator cuff tears (RCT) are among the most common causes of shoulder dysfunction, frequently leading to chronic pain and impaired muscle performance. To gain deeper insight into the molecular mechanisms underlying this condition, proteomic approaches offer an unbiased means of characterizing global protein expression changes. In this study, we compared the proteomic profiles of healthy gracilis muscle and rotator cuff tear (RCT) tissue using label-free quantitative proteomics, with the aim of identifying differentially expressed proteins that may serve as biomarkers or provide mechanistic insight into disease progression.