Upregulation of microRNA‐9‐5p inhibits apoptosis of chondrocytes through downregulating Tnc in mice with osteoarthritis following tibial plateau fracture

Chen, Hongwei; Yang, Jun; Tan, Zhihong

doi:10.1002/jcp.28900

Cited by 22 publications

(13 citation statements)

References 42 publications

(60 reference statements)

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“…Herein, consistently, we reported that miR-9-5p was highly expressed in OA models in vitro, and additionally, it was found that miR-9-5p could reverse the protective role of MEG3 on chondrocytes, suggesting that miR-9-5p was an injurious factor during OA progression. However, a previous study finds that, in the cartilage of OA mice following tibial plateau fracture, miR-9-5p can suppress chondrocyte apoptosis and promote cartilage remodeling (Chen et al, 2019b), which is different from our study. The reason might be that the previous study constructs a mouse model of traumatic osteoarthritis, while FIGURE 5 | MiR-9-5p could reverse the effects of MEG3 on chondrocytes.…”

Section: Discussioncontrasting

confidence: 99%

“…miRNAs are a class of small non-coding RNAs, abnormally expressed in OA, and are pivotal regulators in the proliferation, apoptosis, osteogenic differentiation, and inflammatory response of chondrocytes during OA pathogenesis (Swingler et al, 2012). It is reported that miR-9-5p can inhibit chondrocyte apoptosis and promote cartilage remodeling in OA (Chen et al, 2019a). The underlying regulatory between MEG3 and miR-9-5p warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

et al. 2021

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BackgroundOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammatory changes. This work aims to investigate the protective role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) against the apoptosis of chondrocytes.MethodsChondrocyte cell lines, CHON-001, and ATDC5 were treated with different doses of interleukin-1β (IL-1β) to mimic the inflammatory response during OA pathogenesis. Quantitative real-time polymerase chain reaction was performed to measure MEG3, miR-9-5p, and Krüppel-like factor 4 (KLF4) mRNA expression levels. MEG3 and KLF4 overexpression plasmids, MEG3 shRNA, miR-9-5p mimics, and miR-9-5p inhibitors were transfected into the cells. Cell counting kit-8, wound healing assay, and flow cytometry were conducted to determine cell viability, migration, and apoptotic rate. Dual-luciferase reporter assay was adopted to verify the targeting relationships among MEG3, miR-9-5p, and KLF4. Western blot was used to detect KLF4 protein expression. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors.ResultsMEG3 expression in chondrocytes was down-regulated by the stimulation of IL-1β, and MEG3 negatively regulated miR-9-5p expression but positively regulated KLF4 expression. MEG3 overexpression strengthened the viability and migration of CHON-001 and ATDC5 cells but restrained the apoptosis and inflammatory response, while MEG3 knockdown had opposite effects. miR-9-5p inhibition or KLF4 overexpression could counteract the effects of MEG3 knockdown on chondrocytes. Besides that, MEG3 was proved to be a molecular sponge for miR-9-5p, and KLF4 was verified as the target of miR-9-5p.ConclusionMEG3 can promote chondrocyte proliferation and migration and inhibit apoptosis and inflammation by sponging miR-9-5p to induce KLF4 expression, which provides a promising therapy target for OA treatment.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

et al. 2021

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“…For example, miRNA (miR)-103 restrained chondrocyte proliferation by targeting Sox6 to trigger OA progression ( 10 ). Additionally, miR-9-5p overexpression hindered chondrocyte apoptosis by inhibiting tenascin C expression in a mouse model of OA ( 11 ). In addition, miR-21-5p upregulated collagen type II-α1 chain expression to facilitate cartilage formation in interleukin (IL)-1β-induced chondrocytes ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Yuan

Song

et al. 2020

Exp Ther Med

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Osteoarthritis (OA) is a joint disease caused by a variety of factors, including aging, obesity and trauma. MicroRNAs (miRNAs) have been reported to be crucial regulators during OA progression. The present study aimed to investigate the role of miR-17-5p and miR-19b-3p during OA development. Interleukin (IL)-1β-treated chondrocytes were used to mimic OA in vitro. The expression levels of miR-17-5p and enhancer of zeste homolog 2 (EZH2) were measured in cartilage tissues and chondrocytes using reverse transcription-quantitative PCR or western blotting. Apoptosis was assessed by flow cytometry. The protein expression levels of extracellular matrix (ECM)-associated genes were detected by western blotting. The binding sites between miR-17-5p or miR-19b-3p and EZH2 were predicted using the MicroT-CDS online database and verified using dual-luciferase reporter and RIP assays. miR-17-5p expression was downregulated, whereas EZH2 expression was upregulated in OA cartilage tissues and IL-1β-induced chondrocytes compared with that in the control tissues and cells. miR-17-5p mimics inhibited IL-1β-induced apoptosis and ECM degradation in chondrocytes. EZH2 was the target of miR-17-5p and miR-19b-3p in chondrocytes, and enhanced apoptosis and ECM degradation in IL-1β-stimulated chondrocytes. Rescue experiments revealed that miR-17-5p or miR-19b-3p mimic-induced inhibition of OA progression was reversed by EZH2 overexpression. In conclusion, miR-17-5p and miR-19b-3p inhibited OA progression by targeting EZH2, which may serve as a potential therapeutic target for OA.

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“…The expression analysis of top 10 candidate marker genes in different types of chondrocyte also showed TNFAIP6, GAS1, SLC7A2 and TNC were high expression in HTCs. TNFAIP6, GAS1 and TNC have been found associated with the biological function of chondrocyte or cartilage by other researchers [37][38][39]. The change in expression level of these genes in HTCs of OAs can be used to judge the development status of OA.…”

Section: Discussionmentioning

confidence: 96%

Single-cell RNA seq analysis identifies the biomarkers and differentiation of chondrocyte in human osteoarthritis

Zhang

Huang

et al. 2020

Preprint

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Background： Single-cell RNA sequencing (scRNA-seq) was recently adopted for exploring molecular programmes and lineage progression patterns of pathogenesis of important diseases. In this study, scRNA-seq was used to identify potential markers for chondrocytes in osteoarthritis (OA) and to explore the function of different types of chondrocytes in OA.Methods：Here we aimed to identify the biomarkers and differentiation of chondrocyte by Single-cell RNA seq analysis. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify the function of candidate marker genes in chondrocytes. Protein–protein interaction (PPI) network was constructed to find the hub genes in 3 types of chondrocyte respectively. We also used qRT-PCR to detect the expression level of the candidate marker genes in different types of chondrocyte. Results： In this study, we characterized the single-cell expression profiling of 480 chondrocyte samples and found hypertrophic chondrocyte (HTC), homeostatic chondrocyte (HomC) and fibrocartilage chondrocyte (FC) respectively. The results of GO and KEGG analysis showed the candidate marker genes made specific function in these chondrocytes to regulate the development of OAs respectively. We further revealed the differential expression of top 10 marker genes in 3 types of chondrocyte. The marker genes of HTC and FC were mainly expressed in their cell subset respectively. The marker genes of HomC did not have obviously differential expression among different types of chondrocyte. Last, we predicted the key genes in each cell subset. CD44, JUN and FN1 were predicted tightly related to the proliferation and differentiation of chondrocytes in OAs and could be regarded as biomarkers to estimate the development of OA. Conclusion： Our results provide new insights into exploring the roles of different types of chondrocyte in OA. The biomarkers of chondrocyte were also valuable for estimating OA progression.

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Upregulation of microRNA‐9‐5p inhibits apoptosis of chondrocytes through downregulating Tnc in mice with osteoarthritis following tibial plateau fracture

Cited by 22 publications

References 42 publications

LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

miR‑17‑5p and miR‑19b‑3p prevent osteoarthritis progression by targeting EZH2

Single-cell RNA seq analysis identifies the biomarkers and differentiation of chondrocyte in human osteoarthritis

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