Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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]

ABSTRACT: 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

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE241201 | GEO | 2023/11/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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

Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype

Project description:Aged tendons have disrupted homeostasis, increased injury risk, and impaired healing capacity. Understanding mechanisms of homeostatic disruption is crucial for developing therapeutics to retain tendon health through the lifespan. Here, we developed a novel model of accelerated tendon extracellular matrix (ECM) aging via depletion of Scleraxislineage (ScxLin) cells in young mice (DTR). DTR recapitulates many aspects of tendon aging including comparable declines in cellularity, alterations in ECM structure, organization, and composition. Single cell RNA-sequencing demonstrated a conserved decline in tenocytes associated with ECM biosynthesis in aged and DTR tendons, identifying the requirement for ScxLin cells during homeostasis. However, the remaining cells in aged and DTR tendons demonstrate functional divergence. Aged tenocytes become pro-inflammatory and lose proteostasis. In contrast, DTR tenocytes demonstrate enhanced remodeling capacity. Collectively, this study defines DTR a novel model of accelerated tendon ECM aging and identifies novel biological intervention points to maintain tendon function through the lifespan

2023-02-01 | GSE214929 | GEO

Scleraxis-lineage cells are required for tendon homeostasis and their depletion induces an accelerated extracellular matrix aging phenotype

Project description:Aged tendons have disrupted homeostasis, increased injury risk, and impaired healing capacity. Understanding mechanisms of homeostatic disruption is crucial for developing therapeutics to retain tendon health through the lifespan. Here, we developed a novel model of accelerated tendon extracellular matrix (ECM) aging via depletion of Scleraxis-lineage (ScxLin) cells in young mice (DTR). DTR recapitulates many aspects of tendon aging including comparable declines in cellularity, alterations in ECM structure, organization, and composition. Single cell RNA-sequencing demonstrated a conserved decline in tenocytes associated with ECM biosynthesis in aged and DTR tendons, identifying the requirement for ScxLin cells during homeostasis. However, the remaining cells in aged and DTR tendons demonstrate functional divergence. Aged tenocytes become pro-inflammatory and lose proteostasis. In contrast, DTR tenocytes demonstrate enhanced remodeling capacity. Collectively, this study defines DTR a novel model of accelerated tendon ECM aging and identifies novel biological intervention points to maintain tendon function through the lifespan.

2023-02-03 | PXD037230 | Pride

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

2015-07-10 | GSE68485 | GEO

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

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

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

2021-10-02 | GSE181172 | GEO

Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects

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

N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/β1/PI3K/AKT signaling

Project description:N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biological functions of tendon stem/progenitor cells (TSPCs) and tendon repair has not been clarified.The effect of NAC on gene transcription in TSPCs was analyzed by transcriptomes and bioinformatics.

2022-11-18 | GSE218038 | GEO

Tenomodulin prevents trauma-induced heterotopic ossification in tendon

Project description:We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this together with augmented HO resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.

2021-11-08 | GSE179454 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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