Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition [array]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE180368 | GEO | 2021/10/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition [seq]

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

Analysis of Human Tendinopathy Gene Expression

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

Analysis of Human Tendinopathy Gene Expression

2011-06-07 | GSE26051 | GEO

miRNA microarray of rTDSCs under mechanical treatment or not

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

A quantitative label-free analysis of the extracellular proteome of human supraspinatus reveals damage to the pericellular and elastic fibre niches in torn and aged tendons

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

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration capacity via rejuvenating senescent tendon stem/progenitor cells [DMSO-treated and POG-treated Passage 12 TSPCs]

Project description:Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC- senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore self-renewal and proliferation capacities, and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescues endogenous tendon regeneration and repair capacity in aged rats to levels similar to normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and downregulating mTOR signaling with induction of autophagy. Together, the strategy by pharmacological intervention with deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons. We performed mRNA microarray analyses of DMSO-treated and POG-treated Passage 12 TSPCs and identified meaningful genes in down-regulated and up-regulated group

2023-11-02 | GSE241201 | GEO

Expression data from rat Achilles tendon-derived stem cells during development

Project description:We have compared the gene expression profile of rat Achilles tendon-derived stem cells in post-natal tendon development. Rat tendon stem/progenitor cells (TSPCs) were isolated at different stages of post-natal development: TSPCs-1d, TSPCs-7d and TSPCs-56d. TSPCs at different post-natal development stages (1d, 7d and 56d) were isolated, cultured and used for microarray analyses at passage 2. All TSPCs in this study were of isolated from more than one individual. Total RNA was extracted and fragmented biotin-tagged cRNA was hybridized to Rat Genome 230 2.0 Array.

2015-07-10 | E-GEOD-68485 | biostudies-arrayexpress

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration capacity via rejuvenating senescent tendon stem/progenitor cells [DMSO-treated and POG-treated TSPCs]

Project description:Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC- senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore self-renewal and proliferation capacities, and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescues endogenous tendon regeneration and repair capacity in aged rats to levels similar to normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and downregulating mTOR signaling with induction of autophagy. Together, the strategy by pharmacological intervention with deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons. We performed mRNA microarray analyses of DMSO-treated and POG-treated TSPCs from 18-month-old rats and identified meaningful genes in down-regulated and up-regulated group

2023-11-02 | GSE241202 | GEO

Comparison of Protein Extraction Methods in Tendon Mass Spectrometry Analysis

Project description:Tendons play a fundamental role in the musculoskeletal system and locomotion by transferring forces generated from muscles to the skeleton. Tendon injuries can occur due to sports related incidents, as a result of trauma to overuse or during disease or ageing. Using proteomic techniques tendon protein profiles could be defined under different conditions. The aim of this study was to optimise tendon sample preparation for mass spectrometry analysis, which will be valuable for future tendon studies.

2018-07-05 | PXD004453 | Pride

Expression data from rat Achilles tendon-derived stem cells during development

2015-07-10 | GSE68485 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data