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.
Project description:Platelet-rich plasma (PRP) is used to treat musculoskeletal diseases, such as rotator cuff tears, and has been proven to attenuate fatty infiltration in muscle injury; however, the effective components are still unclear. In this study, we found that young donor-derived exosomes were critical components in PRP that regulate fatty infiltration in muscle injury by directly inhibiting adipogenesis of muscle-resident FAPs.
Project description:Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. 3D printing, a promising technology, enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multi-differentiation potential and valuable immunomodulatory effects. Basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed PCL scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks post-surgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.
Project description:Musculoskeletal injuries related to the rotator cuff (RC) are frequent and account for up to 70% of shoulder pain problems. Lesions of the RC lead to weakness and pain (ref: Carr et al mfl) and untreated these lesions are acompanied by muscle degeneration modulated by inflammatory reactions that vary in intensity. Anti-inflammatory modalities such as NSAID and corticosteroids are commonly used as add ons to conservative treatment of RC tendon tears or RC tendon surgery, which are, however associated with high failure rates. The aim was to study the impact that a conventional TNF inhibitor and a super selective TNF inhibitor (Anti-TNF treatment) has on soft tissue inflammation and bone constituent parameters/connective tissue in a rotator cuff tear model.
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: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.
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:We found that lactate and lactylation were significantly elevated in rotator cuff tears, and lactylation primarily regulates histones in tenocytes. Therefore, we screened for histone lactylation and identified that H3K9, H4K8, and H4K16 had the most prominent increases. Subsequently, we conducted CUT - Tag assays on them. The results indicated that H3K9la was enriched at the promoters of ENO3 and COL1, while H4K16la was enriched at the promoter of TNMD, which induced the transcriptional expression of these genes. Moreover, as a glycolytic enzyme, ENO3 is further involved in the H3K9la–Eno3–lactate–H3K9la positive feedback loop to maintain a high lactate level. This feedback loop continuously drives the H3K9 - COL1 and H4K16 - TNMD regulatory axes, ultimately promoting the repair of rotator cuff tear injuries.
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.