Dataset Information

Circ0083429 Regulates Osteoarthritis Progression via the Mir-346/SMAD3 Axis.

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease. Currently, apart from symptomatic treatment or joint replacement, no other effective treatments for OA exist. The mechanisms underlying OA remain elusive and require further research. Circular RNAs (circRNAs) are known to be involved in many diseases; however, their function in OA is not yet fully understood. Here, we identified a novel circRNA, Circ0083429. The role of Circ0083429 in OA was confirmed via western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence (IF) through knockdown and overexpression experiments. The binding of Circ0083429 to downstream miR-346 and its target gene SMAD3 was predicted via bioinformatics analysis and verified using a luciferase reporter assay and RNA pulldown experiments. Finally, the function of Circ0083429 was evaluated in mouse OA models. In our study, we found that Circ0083429 regulates the homeostasis of the extracellular matrix (ECM) in human chondrocytes. Mechanistically, Circ0083429 affects OA by regulating the mRNA level of SMAD3 through the sponging of microRNA (miRNA)-346. Injecting adeno-associated virus Circ0083429 into the intra-junction of the mouse knee alleviated OA. In conclusion, Circ0083429 regulates the ECM via the regulation of the downstream miRNA-346/SMAD3 in human chondrocytes, which provides a new therapeutic strategy for OA.

SUBMITTER: Yao T

PROVIDER: S-EPMC7843588 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circ0083429 Regulates Osteoarthritis Progression via the Mir-346/<i>SMAD3</i> Axis.

Yao Teng T Yang Yute Y Xie Ziang Z Xu Yining Y Huang Yizhen Y Gao Jun J Shen Shuying S Ye Huali H Iranmanesh Yasaman Y Fan Shunwu S Ma Jianjun J

Frontiers in cell and developmental biology 20210115

Osteoarthritis (OA) is a degenerative joint disease. Currently, apart from symptomatic treatment or joint replacement, no other effective treatments for OA exist. The mechanisms underlying OA remain elusive and require further research. Circular RNAs (circRNAs) are known to be involved in many diseases; however, their function in OA is not yet fully understood. Here, we identified a novel circRNA, Circ0083429. The role of Circ0083429 in OA was confirmed via western blot (WB), quantitative real-t ...[more]

PMID: 33520980

Similar Datasets

Project description:Osteoarthritis (OA) is a common articular degenerative disease characterized by loss of cartilage matrix and subchondral bone sclerosis. Kartogenin (KGN) has been reported to improve chondrogenic differentiation of mesenchymal stem cells. However, the therapeutic effect of KGN on OA-induced cartilage degeneration was still unclear. This study aimed to explore the protective effects and underlying mechanisms of KGN on articular cartilage degradation using mice with post-traumatic OA. To mimic the in vivo arthritic environment, in vitro cultured chondrocytes were exposed to interleukin-1β (IL-1β). We found that KGN barely affected the cell proliferation of chondrocytes; however, KGN significantly enhanced the synthesis of cartilage matrix components such as type II collagen and aggrecan in a dose-dependent manner. Meanwhile, KGN markedly suppressed the expression of matrix degradation enzymes such as MMP13 and ADAMTS5. In vivo experiments showed that intra-articular administration of KGN ameliorated cartilage degeneration and inhibited subchondral bone sclerosis in an experimental OA mouse model. Molecular biology experiments revealed that KGN modulated intracellular reactive oxygen species in IL-1β-stimulated chondrocytes by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2), while barely affecting its mRNA expression. Microarray analysis further revealed that IL-1β significantly up-regulated miR-146a that played a critical role in regulating the protein levels of NRF2. KGN treatment showed a strong inhibitory effect on the expression of miR-146a in IL-1β-stimulated chondrocytes. Over-expression of miR-146a abolished the anti-arthritic effects of KGN not only by down-regulating the protein levels of NRF2 but also by up-regulating the expression of matrix degradation enzymes. Our findings demonstrate, for the first time, that KGN exerts anti-arthritic effects via activation of the miR-146a-NRF2 axis and KGN is a promising heterocyclic molecule to prevent OA-induced cartilage degeneration.

Dataset Information

Circ0083429 Regulates Osteoarthritis Progression via the Mir-346/SMAD3 Axis.

Publications

Circ0083429 Regulates Osteoarthritis Progression via the Mir-346/<i>SMAD3</i> Axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets