Exosome miR-4738-3p-mediated regulation of COL1A2 through the NF-κB and inflammation signaling pathway alleviates osteoarthritis low-grade inflammation symptoms

• Published in: Biomolecules & biomedicine Vol. 24; no. 3; pp. 520 - 536
• Main Authors: Xu, Jun, Zhou, Kaifeng, Gu, Huijie, Zhang, Yiming, Wu, Liang, Bian, Chong, Huang, Zhongyue, Chen, Guangnan, Cheng, Xiangyang, Yin, Xiaofan
• Format: Journal Article
• Language: English
• Published: Bosnia and Herzegovina Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 02.05.2024
• Subjects: Cell Line; Collagen Type I - genetics; Collagen Type I - metabolism; collagen type I alpha 2 chain (COL1A2); Exosome; Exosomes - genetics; Exosomes - metabolism; Gene Expression Regulation; Humans; Inflammation - genetics; Inflammation - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; micro RNA (miR)-4739-3p; MicroRNAs - genetics; MicroRNAs - metabolism; NF-kappa B - metabolism; nuclear factor kappa B (NF-κB) signaling pathway; osteoarthritis (OA); Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Signal Transduction - genetics
• ISSN: 2831-0896; 2831-090X; 2831-090X
• DOI: 10.17305/bb.2023.9921

This study aimed to elucidate the roles of microRNA (miR)-4738-3p and the collagen type I alpha 2 chain (COL1A2) gene in the pathogenesis of osteoarthritis (OA) through bioinformatics analysis and cellular assays. The GSE55235 dataset was analyzed using the weighted gene co-expression network analysis (WGCNA) method to identify gene modules associated with OA. Key overlapping genes were identified from these modules and the GSE55235-differential expressed genes (DEGs). The expression levels of selected genes were determined in C28/I2 cells using the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-4738-3p and COL1A2 was examined in the context of interleukin 1 beta (IL-1β) induction. Exosome characterization was achieved through transmission electron microscopy (TEM), western blotting (WB), and other analyses. The study also investigated the functional relevance of miR-4738-3p in OA pathology through various molecular and cellular assays. Our findings revealed that the green module exhibited a strong correlation with the OA phenotype in the GSE55235 dataset, with COL1A2 emerging as a hub gene and miR-4738-3p as its key downstream target. IL-1β induction suggested that COL1A2 is involved in inflammation and apoptosis, while miR-4738-3p appeared to play an antagonistic role. The analysis of exosomes underscored the significance of miR-4738-3p in cellular communication, with an enhanced level of exo-miR-4738-3p antagonizing IL-1β-induced inflammation and promoting cell survival. Conversely, a reduction in exo-miR-4738-3p led to increased cell damage. This study established a clear regulatory relationship between miR-4738-3p and COL1A2, with the nuclear factor kappa B (NF-κB) signaling pathway playing a central role in this regulation. The miR-4738-3p significantly influences the OA-associated inflammation, primarily through modulation of COL1A2 and the NF-κB pathway. Therefore, targeting miR-4738-3p offers a potential therapeutic approach for OA, with exosome miR-4738-3p presenting a promising strategy.