KDM3A Modulates Biological Processes in Osteoarthritis Cell Models Via the Wnt/β-Catenin Signaling Pathway.

Abstract

BackgroundOsteoarthritis (OA) is a chronic disease that seriously affects human health. Although biomarkers are vital to the discovery and therapy of OA, current research on OA-specific biomarkers remains limited, indicating a need for further expansion of this field of study.MethodsIn this study, differential genes in OA patients and normal samples in Genomics Expression Omnibus (GEO) database were analyzed for signaling pathway enrichment. Then, Weighted Gene Co-expression Network Analysis (WGCNA) combined with Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to obtain key genes associated with OA diagnosis, including BCL6 co-repressor (BCOR), Coiled-Coil Domain Containing 59 (CCDC59), Jun Proto-Oncogene (JUN), Lysine Demethylase 3A (KDM3A), L3MBTL Histone Methyl-Lysine Binding Protein 4 (L3MBTL4) and Zinc Finger Protein 292 (ZNF292). Finally, the role of KDM3A in OA cell model was verified by constructing KDM3A overexpression and silencing cell lines.ResultsIt was found that overexpression of KDM3A significantly downregulated β-catenin expression compared with the oe-NC group, thus affecting a series of biological processes in the OA cell model, specifically, increasing antioxidant capacity, reducing levels of inflammatory factors, and inhibiting extracellular matrix degradation.ConclusionThis study not only provided six key target genes for OA but also revealed the important role of KDM3A in OA, providing a reference for gene targeted therapy for OA patients.