Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MicroRNA-10a-3p Improves Cartilage Degeneration by Regulating CH25H-CYP7B1-RORα Mediated Cholesterol Metabolism in Knee Osteoarthritis Rats.

ABSTRACT: Osteoarthritis (OA) is a worldwide degenerative joint disease that seriously impaired the quality of life of patients. OA has been established as a disease with metabolic disorder. Cholesterol 25-hydroxylase (CH25H) was proved to play a key role in cartilage cholesterol metabolism. However, the biological function and mechanism of CH25H in OA remains further investigation. Growing researches have proved the vital roles of miRNAs in OA progression. In this study, we screened out miR-10a-3p through high-throughput miRNA sequencing which may bind to CH25H. Molecular mechanism investigation indicated that miR-10a-3p is an upstream target of CH25H. Functional exploration revealed miR-10a-3p suppressed the inflammatory responses, cholesterol metabolism and extracellular matrix (ECM) degradation in primary chondrocytes. Moreover, rescue assays implied that miR-10a-3p reversed CH25H plasmids induced inflammatory cytokine production and ECM degradation. Furthermore, the OA rat model was established to explore the function of miR-10a-3p in vivo. The results showed that miR-10a-3p can recover the OA features through targeting CH25H/CYP7B1/RORα axis. In conclusion, these findings implied a crucial role of miR-10a-3p/CH25H/CYP7B1/RORα axis in OA, which may provide a promising therapeutic strategy for OA.

SUBMITTER: Li X

PROVIDER: S-EPMC8209416 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Role of circNFKB1 in cartilage degeneration of knee osteoarthritis and its mechanism

Project description:Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules produced by reverse splicing of the precursor mRNAs of thousands of gene exons in eukaryotes. Some circRNAs play potentially important roles at the molecular level through different modes of action in physiological and pathological conditions. In recent years, it has been found that differentially expressed circRNAs are present in chondrocyte degeneration in OA and are able to modulate the inflammatory response in chondrocyte degeneration. However, the molecular mechanisms of how circRNAs regulate the inflammatory response during chondrogenic degeneration in OA have not been adequately studied. Are there other circRNAs involved in regulating the inflammatory response during knee OA chondrocyte degeneration and are there other molecular mechanisms by which circRNAs regulate chondrocyte degeneration? These scientific questions deserve relevant studies.

2022-10-15 | PXD033469 | Pride

HPIP controls osteoarthritis cartilage degeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-23 | GSE100312 | GEO

Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration.

Project description:The hereditary spastic paraplegias (HSPs) are a genetically and clinically heterogeneous group of upper-motor-neuron degenerative diseases characterized by selective axonal loss in the corticospinal tracts and dorsal columns. Although numerous mechanisms involving defective subcellular transportation, mitochondrial malfunction, and increased oxidative stress have been proposed, the pathogenic basis underlying the neuronal loss is unknown. We have performed linkage analysis to refine the extent of the SPG5 disease locus and conducted sequence analysis of the genes located within this region. This identified sequence alterations in the cytochrome P450-7B1 (CYP7B1) associated with this pure form of HSP. In the liver, CYP7B1 offers an alternative pathway for cholesterol degradation and also provides the primary metabolic route for the modification of dehydroepiandrosterone neurosteroids in the brain. These findings provide the first direct evidence of a pivotal role of altered cholesterol metabolism in the pathogenesis of motor-neuron degenerative disease and identify a potential for therapeutic intervention in this form of HSP.

| S-EPMC2426914 | biostudies-literature

RNA-seq from knee and hip osteoarthritis cartilage

Project description:In total, 70 samples on macroscopically preserved and lesioned OA cartilage from the same patient was taken for RNA-seq. Subsequently, paired-end 2×100 bp RNA library sequencing (Illumina TruSeq RNA Library Prep Kit, Illumina HiSeq 2000 and TruSeq Stranded Total RNA LT Sample Prep Kit, Illumina HiSeq 4000) was performed.

2019-01-07 | E-MTAB-7313 | biostudies-arrayexpress

Zhuangguguanjie formulation protects articular cartilage from degeneration in joint instability-induced murine knee osteoarthritis.

Project description:Zhuangguguanjie formulation (ZG) can provide noticeable relief from joint pain in patients suffering from knee osteoarthritis (OA). However, the underlying mechanism has not been fully described. Male C57BL/6 mice were administered either ZG or normal saline (NS) following surgical destabilization of the medial meniscus (DMM). At weeks 4, 6 and 8 (post-surgery), knee joints were harvested and assessed with Safranin-O staining. Blood serum was collected and tested. In vitro analysis was carried out to evaluate the effects of ZG on the expression of the OA-related genes. DMM mice indicated reduced cartilage destruction and lower blood serum biomarkers of OA (COMP1 and CTX-1) following ZG treatment. Moreover, the femoral condyle and tibial plateau histological scores were significantly reduced following ZG treatment of the DMM mice. ZG could markedly downregulate the expression of OA-related genes namely, ADAMTS5, MMP3 and MMP13, while it simultaneously upregulated collagen II as demonstrated by in vitro assays. Moreover, chondrocyte apoptosis was significantly decreased following ZG treatment. These results may be caused by the up-regulation of p-AKT expression levels, since the anti-apoptotic effects of ZG can be blocked by treatment with an AKT inhibitor. ZG is capable of preventing and/or reducing the progression of OA by inhibiting chondrocyte apoptosis via the p-AKT/Caspase 3 pathway.

| S-EPMC5835806 | biostudies-literature

HPIP controls osteoarthritis cartilage degeneration

Project description:HPIP controls osteoarthritis cartilage degeneration

| PRJNA391300 | ENA

HPIP controls osteoarthritis cartilage degeneration [ChIP-seq]

Project description:To assess the direct downstream targets of HPIP, a genome-wide ChIP-seq profiling was performed. The ChIP-seq data was examined by the quality evaluation. The results demonstrated that of significant ChIP-seq peaks for HPIP, 59% of them occurred at intronic and intergenic sites We found HPIP was closely correlated with the cartilage development.

2017-06-23 | GSE100311 | GEO

HPIP controls osteoarthritis cartilage degeneration [RNA-seq]

Project description:To underly the potential downstream transcriptional regulation of HPIP that could account for cartilage and skeletal development. RNA-seq analysis were performed in HPIP knockout and control primary chondrocytes.Among the 1271 significantly differentially expressed genes, transcripts for 486 (7%) of them were upregulated while transcripts for 785 (11%) were downregulated in HPIP knockout chondrocytes compared to the controls. We found HPIP was closely correlated with the cartilage development.

2017-06-23 | GSE100268 | GEO

NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis

Project description:Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response through mechanical loading-sensitive signaling networks including ERK 1/2. The objective of this study is to define the role of NG2/CSPG4 in the initiation and progression of TMJ OA and to determine if NG2/CSPG4 engages ERK 1/2 in a mechanical loading dependent manner. In vivo, we induced TMJ OA in control and NG2/CSPG4 knockout mice using a surgical destabilization approach. In control mice, NG2/CSPG4 is depleted during the early stages of TMJ OA and NG2/CSPG4 knockout mice have more severe cartilage degeneration, elevated expression of key OA proteases, and suppression of OA matrix synthesis genes. In vitro, we characterized the transcriptome and protein from control and NG2/CSPG4 knockout cells and found significant dysregulation of the ERK 1/2 signaling axis. To characterize the mechanobiological response of NG2/CSPG4, we applied mechanical loads on cell-agarose-collagen scaffolds using a compression bioreactor and illustrate that NG2/CSPG4 knockout cells fail to mechanically activate ERK 1/2 and are associated with changes in the expression of the same key OA biomarkers measured in vivo. Together, these findings implicate NG2/CSPG4 in the mechanical homeostasis of TMJ cartilage and in the progression of degenerative arthropathies including OA.

2022-09-24 | GSE214077 | GEO

Knee cartilage loss in symptomatic knee osteoarthritis over 4.5 years.

Project description:The objective of this study was to describe the rate of change in knee cartilage volume over 4.5 years in subjects with symptomatic knee osteoarthritis (OA) and to determine factors associated with cartilage loss. One hundred and five subjects were eligible for this longitudinal study. Subjects' tibial cartilage volume was assessed by magnetic resonance imaging (MRI) at baseline, at 2 years and at 4.5 years. Of 105 subjects, 78 (74%) completed the study. The annual percentage losses of medial and lateral tibial cartilage over 4.5 years were 3.7 +/- 4.7% (mean +/- SD; 95% confidence interval 2.7 to 4.8%) and 4.4 +/- 4.7% (mean +/- SD; 95% confidence interval 3.4 to 5.5%), respectively. Cartilage volume in each individual seemed to track over the study period, relative to other study participants. After multivariate adjustment, annual medial tibial cartilage loss was predicted by lesser severity of baseline knee pain but was independent of age, body mass index and structural factors. No factors specified a priori were associated with lateral cartilage volume rates of change. Tibial cartilage declines at an average rate of 4% per year in subjects with symptomatic knee OA. There was evidence to support the concept that tracking occurs in OA. This may enable the prediction of cartilage change in an individual. The only significant factor affecting the loss of medial tibial cartilage was baseline knee pain, possibly through altered joint loading.

| S-EPMC1779368 | biostudies-other

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