RNA-seq of rat Achilles tendon tissue from pefloxacin and/or dexamethasone treated animals
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE212344 | GEO | 2023/04/12
REPOSITORIES: GEO
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Project description:Tendinopathy, the most common disorder affecting tendons, is characterized by chronic disorganization of the tendon matrix, which eventually leads to tendon tear and rupture. The goal of this study was to identify a rational molecular target whose blockade can serve as a potential therapeutic intervention for tendinopathy. We identified C1q/TNF-related protein-3 (CTRP3) as a markedly upregulated cytokine in human and rodent tendinopathy. Overexpression of CTRP3 enhanced the progression of tendinopathy by accumulating cartilaginous proteoglycans and degenerating collagenous fibers in the mouse tendon, whereas CTRP3 knockdown suppressed the tendinopathy pathogenesis. Functional blockade of CTRP3 using a neutralizing antibody ameliorated overuse-induced tendinopathy of the Achilles and rotator cuff tendons. Mechanistically, CTRP3 elicited a transcriptomic pattern that stimulates abnormal differentiation of tendon stem/progenitor cells (TSPCs) and ectopic chondrification in tendons, as an effect linked to activation of Akt signaling. Collectively, we reveal an essential role for CTRP3 in tendinopathy and propose a potential therapeutic strategy for the treatment of tendinopathy.
2021-10-02 | GSE181172 | GEO
Project description:Tendinopathy, the most common disorder affecting tendons, is characterized by chronic disorganization of the tendon matrix, which eventually leads to tendon tear and rupture. The goal of this study was to identify a rational molecular target whose blockade can serve as a potential therapeutic intervention for tendinopathy. We identified C1q/TNF-related protein-3 (CTRP3) as a markedly upregulated cytokine in human and rodent tendinopathy. Overexpression of CTRP3 enhanced the progression of tendinopathy by accumulating cartilaginous proteoglycans and degenerating collagenous fibers in the mouse tendon, whereas CTRP3 knockdown suppressed the tendinopathy pathogenesis. Functional blockade of CTRP3 using a neutralizing antibody ameliorated overuse-induced tendinopathy of the Achilles and rotator cuff tendons. Mechanistically, CTRP3 elicited a transcriptomic pattern that stimulates abnormal differentiation of tendon stem/progenitor cells (TSPCs) and ectopic chondrification in tendons, as an effect linked to activation of Akt signaling. Collectively, we reveal an essential role for CTRP3 in tendinopathy and propose a potential therapeutic strategy for the treatment of tendinopathy.
2021-10-02 | GSE180368 | GEO
Project description:Tendon is a highly aligned connective tissue, in which the macro-structure consists of collagen-rich fascicles surrounded by interfascicular matrix (IFM). In a series of recent studies in equine tissue, we have demonstrated specialisation of tendon composition, structure and mechanics to achieve the tendon’s functional requirements, specifically reporting extensive specialisation of the IFM region in the energy storing superficial digital flexor tendon. We have also demonstrated loss of functional specialisms with ageing, leading to a hypothesised new paradigm for tendinopathy, focused on the importance of the IFM. However, to date, there have been no studies focused on structure-function specialisation or the IFM in functionally distinct human tendons. Here, we compare the positional anterior tibialis tendon and energy storing Achilles tendon, performing a detailed analysis of the composition and mechanical properties of both fascicle and IFM regions, to test the hypothesis that the IFM in the energy storing Achilles tendon has specialised composition and mechanical properties, and that these specialisations are lost with ageing. We demonstrate that the IFM is specialised in the energy storing Achilles tendon, with greater elasticity and fatigue resistance than in the positional anterior tibialis tendon. While there were few age-related alterations in mechanics, we did identify age-related alterations in the IFM proteome of the Achilles tendon specifically, which is predicted to be regulated by TGF-beta signalling and may be responsible for the trend towards decreased fatigue resistance observed in the Achilles IFM with ageing.
2020-11-11 | PXD018212 | Pride
Project description:Chronic tendon injuries, also known as tendinopathy, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure and yet little is known about the molecular mechanism leading to tendinopathy. We have used histological evaluation and molecular profiling to determine the gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy. Diseased tendons have altered extracellular matrix, fiber disorientation, increased cellular content and vasculature and the absence of inflammatory cells. Global gene expression profiling identified 1783 transcripts with significant different expression patterns in the diseased tendons. Global pathway analysis further suggests altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response. We have identified pathways and genes regulated in tendinopathy samples that will help contribute to the understanding of the disease towards the development of novel therapeutics. A prospective study was initiated to collect tissue from patients undergoing surgery as standard of care for tendinopathy. Biopsies (~3mm^3) of diseased tendons as well as a section of grossly normal appearing tendon were collected from 23 patients. Written informed consent was obtained from all patients prior to any study related procedure.
2011-06-07 | E-GEOD-26051 | biostudies-arrayexpress
Project description:Tendon is a hypocellular tissue that contains functional cable-like units of type I collagen responsible for the transmission of force from muscle to bone. In the setting of injury or disease, patients can develop chronic tendinopathies that are characterized by pain, loss of function and persistent inflammatory changes that are often difficult to treat. Platelet-rich plasma (PRP) has shown promise in the treatment of chronic tendinopathy, but little is known about the mechanisms by which PRP can improve tendon healing. PRP contains many different growth factors and cytokines, and since these proteins can both activate and inhibit various signaling pathways it has been challenging to determine precisely which signaling pathways and cellular responses are most important. Using state-of-the-art bioinformatics tools and genome wide-expression profiling, the purpose of this study was to determine the signaling pathways activated within cultured tendon fibroblasts in response to PRP treatment. Tendon fibroblasts were isolated from rat tail tendons and embedded in 3D type I collagen gels. Cells were treated with PRP or PPP for 24 hours, and total RNA was extracted for hybridization on Affymetrix arrays.
2016-01-12 | E-GEOD-70918 | biostudies-arrayexpress
Project description:Tendinopathy is a common disease in individuals whose tendons suffer from repetitive strains, such as athletes. The lack of knowledge regarding the pathological mechanisms causes inadequate prevention methods and low cure rate of this disease. Repetitive strain injury is thought to be the source of tendinopathy; therefore, we investigate the effect of mechanical loading on tendon and seek the ways to prevent and treat tendinopathy better. In our study, we found that the expression of a mechanosensitive miRNA, miR-337-3p, decreased in tendon-derived stem cells (TDSCs) under uniaxial cyclical mechanical loading with 10% elongation. In addition, miR-337-3p was negatively related to chondro-osteogenic differentiation of TDSCs, in which lower expression was found in human calcified tendons and rat tendinopathy samples.
2018-05-24 | GSE114828 | GEO
Project description:The transcriptome of different tendons varies based on anatomical location and is likely influenced by the biomechanical loading environment. While differences in biologic and mechanical properties of whole tendons have been assessed, less is understood about differences within a tendon along its proximal-distal axis. Therefore, our objective was to determine the characteristics of and relationship between the transcriptomes and mechanical properties of a single tendon.
2022-11-03 | GSE193408 | 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: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. We sought to identify the signals modulated with neural TrkA inhibition. A combination of single cell and spatial transcriptomic analysis was performed on the Achilles injury site of TrkA^F592A animals and compared them to TrkA^WT.
2023-11-27 | GSE245097 | GEO
Project description:Tendons play a critical role in the transmission of forces between muscles and bones, and 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 sex-based differences in tendon morphology, composition and mechanical properties may explain the greater susceptibility of women to develop tendinopathies. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from four month old male and female C57Bl/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. Differences between groups were tested using t-tests (α=0.05). While the Achilles tendons of male mice were approximately 6% larger than female mice (P<0.05), the cell density of female mice was around 19% larger than males (P<0.05). No significant differences in the length (P=0.34), peak force (P=0.86), peak stress (P=0.52) or energy loss during stretch (P=0.94) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins like collagen types I (P=0.30) and III (P=0.68), but female mice had approximately two-fold elevations (P<0.05) in different minor ECM proteins such as fibronectin, periostin, and tenascin. Using microarray analysis, there was no significant differences (P>0.05) in the expression of most major and minor ECM genes, and in the expression of genes involved in tendon fibroblast specification or proliferation. Whole tendon qPCR analysis showed significant expression differences in elastin, scleraxis, and tenomodulin. Cell culture techniques to test the effects of sex-specific extracellular environment on cellular activity show significant differences in gene expression of type I and III collagen, Ki67, scleraxis, and tenomodulin. Histologic analysis demonstrated that males have larger tendon cross-sectional area and lower cell density when compared to females. However, there were no differences between the sexes in the mechanical properties of tendons or in the majority of primary structural extracellular matrix proteins, although elevations were observed in some minor ECM proteins. Microarray analysis also showed no significant sex-based differences in the expression of major genes associated with collagen composition, extracellular components and turnover, and fibroblast proliferation. Cell culture tests of non-autonomous cellular activity show no major signals for ECM synthesis nor fibroblast proliferation. Our results indicate that while male mice expectedly had larger tendons, male and female mice have very similar mechanical properties and biochemical composition, with small increases in minor ECM proteins and proteoglycans in female tendons. The role that these minor ECM proteins and proteoglycans play in tendon repair should be evaluated in future studies. No treatment administered, study done to evaluate normal expression profiles of male and female tenocytes. This analysis is based on a Mouse Gene ST 2.1 strip that was processed in the microarray facility in May 2015 using the wt-pico kit.
2016-08-11 | E-GEOD-85415 | biostudies-arrayexpress