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PROVIDER: PRJNA1283935 | ENA |
REPOSITORIES: ENA
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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.
2024-09-30 | GSE277270 | 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. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards modulating inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes.
2023-07-07 | GSE235861 | GEO
Project description:The biological factors that affect healing after rotator cuff repair (RCR) are not well 63 understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated 64 with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, 65 suggesting it may have a role in the repair process. The purpose of the current study was to 66 determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus 67 tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR) and Tenascin 68 C null (Tnc - -RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR 69 and Tnc - -RCR mice and unoperated shoulders from WT and Tnc - mice. We performed 70 histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc71 mice had severe bone and tendon defects following rotator cuff repair. Tnc- -RCR mice had 72 reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and 73 wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered 74 gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and 75 a downregulation of inflammation and cell cycle pathways. Tnc - mice had similar biomechanical 76 properties after repair as WT. Further research is required to evaluate tissue specific alterations 77 of Tnc, the interactions of Tnc and sex hormone and inflammation pathways as well as possible 78 adjuvants to improve enthesis healing in the setting of reduced TNC function.
2024-09-16 | GSE271514 | 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: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.
2022-03-15 | GSE180836 | GEO
Project description:Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (~40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n=3) and diseased tendon cells (n=3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥ 2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or ‘activated’ fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥ 2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation.
2021-12-05 | GSE190085 | GEO
Project description:Tears of the human supraspinatus tendon are common and often cause painful and debilitating loss of function. Progressive failure of the tendon leading to structural abnormality and tearing is accompanied by numerous cellular and extra-cellular matrix (ECM) changes in the tendon tissue. This proteomics study aimed to compare torn and aged rotator cuff tissue to young and healthy tissue, and provide the first ECM inventory of human supraspinatus tendon generated using label-free quantitative LC-MS/MS. Employing two digestion protocols (trypsin and elastase), we analysed grain-sized tendon supraspinatus biopsies from older patients with torn tendons and from young controls. Our findings confirm measurable degradation of collagen fibrils and associated proteins in old and torn tendons, suggesting a significant loss of tissue organisation. A particularly marked reduction of cartilage oligomeric matrix protein (COMP) raises the possibility of using changes in levels of this glycoprotein as a marker of abnormal tissue, as previously suggested in horse models. Surprisingly, and despite using an elastase digestion for validation, elastin was not detected, raising the possibility that it is not highly abundant in human supraspinatus tendon. Finally, we identified marked changes to the elastic fibre, fibrillin-rich niche and the pericellular matrix. Further investigation of these regions may yield other potential biomarkers and help to explain detrimental cellular processes associated with tendon ageing and tendinopathy.
2018-07-03 | PXD006466 | Pride
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.
2025-09-30 | GSE309143 | GEO
Project description:The hamstring tendon is used as autograft in surgical reconstruction of tears of the anterior cruciate ligament. The rate of re-rupture after surgery is higher in younger patients. The aim of the study was to identify molecular mechanisms that underlie the greater susceptibility of tendon from younger people to tear.
2021-02-23 | GSE167226 | GEO
Project description:Background Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. Methods RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. Results In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. Conclusions We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.
2023-11-02 | GSE236746 | GEO