ArticleJournal of molecular histology2026
CircRNA_02540 alleviated the migration and ligament differentiation capacities of SM-MSCs suppressed by chronic inflammation via regulating miR-203a-3p/ZIC1 pathway.
Article in Journal of molecular histology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Implant of mesenchymal stem cells (MSCs) is a promising therapy for the reconstruction of anterior cruciate ligament (ACL), but the chronic inflammation environment impairs the capacity of MSCs. This study aimed to alleviate the function of synovial membrane-derived MSCs (SM-MSCs) by regulating circRNA and its downstream molecules. In the present study, chronic inflammatory stimulation (TNF-α treatment) weakened the migration and ligament differentiation abilities of SM-MSCs, and reduced the expression level of circRNA_02540, screened from candidates dysregulated in relevant pathological tissues (Jiang et al. in Ann Transl Med 9:1685, 2021; Xiang et al. in J Cell Biochem 120:18031-18040, 2019). Upregulating circRNA_02540 alleviated the functions of SM-MSCs under inflammatory milieu. RNA-sequencing identified 348 differentially expressed genes (DEGs) in circRNA_02540 overexpression group. Bioinformatics analyses screened 23 upregulated DEGs involved in migration and differentiation relevant processes, and used to construct the ceRNA network of circRNA_02540. Next, ZIC1 and miR-203a-3p were screened out. Overexpression of miR-203a-3p or knockdown of ZIC1 inhibited the positive effects of circRNA_02540 on the function of SM-MSCs. Knockdown of ZIC1 inhibited the positive effects exerted by silencing miR-203a-3p on SM-MSC, and overexpression of ZIC1 alleviated the inhibitory effects of miR-203a-3p on the function of SM-MSCs. In conclusion, circRNA_02540 promoted the migration and ligament differentiation abilities of SM-MSCs by sponging miR-203a-3p and enhancing ZIC1 expression, providing a potential solution to enhance the function decline of MSCs used for ACL reconstruction.
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