Interleukin-1b in Tendon Injury Enhances Reparative Gene and Protein Expression in Mesenchymal Stem Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Equus caballus
PROVIDER: GSE208569 | GEO | 2022/07/26
REPOSITORIES: GEO
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Project description:Partial tendon-to-bone interface (TBI) injuries heal in a mechanically inferior manner and redevelop healthy uninjured tissue morphology. The origin of the cells involved in tendon-to-bone healing remains unknown. We employed a rigorous approach to evaluate if mouse skeletal stem cells (mSSC) play a role in tendon-to-bone healing after partial-injury. Using fluorescence-activated cell sorting we identified that found that they are present within the TBI. Using a TBI-injury rainbow lineage tracing mouse model, we demonstrated that injury-responsive cells within the TBI and calcaneus proliferate polyclonally following partial-tendon injury at the TBI. These injury-responsive clonal cells express skeletal marker SP7. We quantified the differences in mSCC frequency after TBI-injury and found that mSSC respond to injury with a higher frequency and have associated changes in gene expression, with the specific down-regulation of the TGFβ signaling pathway. Exogenous delivery of TGFβ after injury was found to reduce the mSSC response after injury. These findings suggest that mSSC may facilitate tendon-to-bone healing by downregulating TGFβ signaling within the mSSC niche.
2022-02-14 | GSE167080 | GEO
Project description:Equine energy-storing SDFT tendon development, Proteomic analysis of IFM and fascicles through development
2021-09-08 | PXD012169 | Pride
Project description:the aim of this study was to isolate, characterise and compare the proteome of the IFM and fascicular matrix (FM) in the equine superficial digital flexor tendon (SDFT). We hypothesised that the proteomic profile would differ between the FM and the IFM, with greater complexity and faster turnover in the IFM. Regions of the SDFT were isolated using laser capture microdissection and the protein profile assessed using mass spectrometry. 246 proteins were identified in the IFM, and 141 were identified in the FM. 60 proteins showed a 2-fold difference in abundance between the IFM and FM, including greater abundance of collagen-III and cellular proteins in the IFM, and higher levels of collagens-I and XII, and fibromodulin in the FM. A greater number of neopeptides were identified in the IFM, indicating more rapid turnover than in the FM. There were few alterations in protein abundance with ageing, but the number of neopeptides decreased with age in the IFM specifically, suggesting a decrease in IFM turnover in aged individuals. These results support the hypothesis, showing distinct protein profiles and indicating more rapid turnover in the IFM than in the FM, which appears to decline with ageing in the IFM specifically. This may result in alterations in IFM mechanical properties in aged tendon, contributing to age-related tendon injury.
2016-02-08 | PXD002979 | Pride
Project description:Little is understood about the roles of tendon cells during flexor tendon healing. To better understand tendon cell functions, the Scx-Cre mouse was crossed to the DTR mouse model to facilitate scleraxis lineage cell depletion prior to acute flexor tendon injury and repair. WT (cre-) and experimental (cre+) mice underwent complete transection and repair of the flexor digitorum longus tendon. Repaired tendons were harvested at 14 and 28 days post-repair for bulk RNA-Seq analysis to examine possible mechanisms driving differential healing due to Scx lineage cell depletion.
2021-02-08 | GSE156157 | 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:We report the newly derived tendon like tissues from human iPSC. We depositted RNA sequencing data of human iPSC and derived MSC from human iPSC. We use these cells as materials to generae tenon-like tissues.
2022-01-10 | GSE193097 | GEO
Project description:Injury was induced in the left Achilles tendon by needle puncture. Rats were sacrificed 4 and 21 days post injury. Shams, in which the tendon was isolated but not punctured, were included as controls. Serum was collected post-mortem and RNAseq used to identify differentially expressed ncRNAs.
2021-03-31 | E-MTAB-9509 | biostudies-arrayexpress
Project description:Here, we investigated the effect of conditioned media (CM) obtained from cultured mouse DRG neurons on Tppp3+ cells, mainly on proliferation and differentiation potential. Peripheral afferent neurons terminate at the surfaces of tendons, yet their role after injury beyond nociceptive functions remain unclear. Using transgenic animal models, sensory neurons were found to sprout after Achilles tendon injury in domains of Nerve growth factor (NGF) expression. Conditional deletion of Ngf in either myeloid or mesenchymal cell types led to tendon repair defects – findings phenocopied by inactivation of TrkA (Tropomyosin receptor kinase A) using a knockin mouse model. A combination of spatial and single cell transcriptomics revealed dysregulated inflammatory and TGF signaling upon lack of neural input. Utilizing sural nerve transection in reporter animals, we identified that neural input is required for proper expansion of Tppp3+ tendon sheath progenitor cells (TSPCs) after injury, and in vitro approaches implicated TGF signaling activation in Tppp3+ TSPC neural response. Finally, in a translational approach, activation of TrkA+ sensory neurons using a partial agonist led to a significant increase in TGF signaling, TSPC expansion, and improved tendon repair. Collectively, these data implicate peripheral afferent neural networks in the coordinated acute tendon injury response, and identify candidate molecules to speed the reparative process.
2023-11-27 | GSE221035 | GEO
Project description:Tendons play fundamental role in the musculoskeletal system and locomotion by transferring forces generated by muscles to the skeleton. Chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that tendon sex-based differences in protein composition are related to an altered injury response. The aim of this study was to compare the proteome of male and female tendon using label-free protein quantification. These data could provide new insight into pathways which may beinvolved in tendinopathies, and potentially in the differential injury response of female tendon.
2017-01-16 | PXD004612 | Pride
Project description:Background: Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods: Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results: In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion: Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.
2022-12-10 | GSE190685 | GEO