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CircBRMS1L Participates in Lipopolysaccharide-induced Chondrocyte Injury via the TLR4/NF-κB Pathway through Serving as a miR-142-5p Decoy

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Abstract

Osteoarthritis (OA) is the main cause of pain and disability in the elderly. It is reported that circular RNA BRMS1L (BRMS1 like transcriptional repressor) (circBRMS1L) is upregulated in the synovial fluid of OA patients. Nevertheless, the biological function of circBRMS1L in OA has not been validated. Lipopolysaccharide (LPS)-induced chondrocytes (C28/I2) were used as OA cell models in vitro. Expression patterns of circBRMS1L, microRNA (miR)-142-5p, and Toll-like Receptor 4 (TLR4) mRNA were verified by quantitative real-time polymerase chain reaction. Loss-of-function experiments were performed to explore the influence of circBRMS1L on LPS-induced extracellular matrix (ECM) degradation, apoptosis, and inflammation in C28/I2 cells. Protein levels were detected by western blotting. The regulatory mechanism of circBRMS1L in OA was explored by bioinformatics analysis, dual-luciferase reporter, RNA immunoprecipitation, and/or RNA pull-down assays. CircBRMS1L was prominently upregulated in OA cartilage tissues and LPS-stimulated C28/I2 cells. Inhibition of circBRMS1L reduced LPS-induced ECM degradation, apoptosis, inflammation, and oxidative stress in C28/I2 cells. MiR-142-5p was downregulated while TLR4 was upregulated in OA cartilage tissues and LPS-stimulated C28/I2 cells. CircBRMS1L adsorbed miR-142-5p to regulate TLR4 expression. MiR-142-5p inhibitor reversed circBRMS1L silencing-mediated effects on LPS-induced ECM degradation, apoptosis, inflammation, and oxidative stress in C28/I2 cells. TLR4 elevation overturned the inhibitory influence of miR-142-5p mimic on LPS-induced ECM degradation, apoptosis, inflammation, and oxidative stress in C28/I2 cells. Notably, circBRMS1L activated the nuclear factor-κB (NF-κB) pathway by the miR-142-5p/TLR4 axis. LPS-induced ECM degradation, apoptosis, inflammation, and oxidative stress in chondrocytes were at least partially regulated by the circBRMS1L/miR-142-5p/TLR4/NF-κB pathway, highlighting a new mechanism responsible for OA advancement.

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  1. Department of Immunology and Rheumatology, Xingtai People’s Hospital, Xingtai, Hebei, 054000, China

    Ronghua Wang, Lianju Li, Jingxu Wang, Xiangzhuo Zhao & Jingfang Shen

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  1. Ronghua Wang
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Correspondence to Lianju Li.

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The authors declare that they have no conflict of interest. The research was reviewed and approved by the Ethics Committee of Xingtai People’s Hospital.

All subjects signed informed consents and then underwent surgical operations at the Xingtai People’s Hospital.

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Wang, R., Li, L., Wang, J. et al. CircBRMS1L Participates in Lipopolysaccharide-induced Chondrocyte Injury via the TLR4/NF-κB Pathway through Serving as a miR-142-5p Decoy. Biotechnol Bioproc E 28, 112–124 (2023). https://doi.org/10.1007/s12257-021-0224-9

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  • DOI: https://doi.org/10.1007/s12257-021-0224-9

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