miR-326 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by targeting NAT10

Abstract Objectives Abnormal osteogenic differentiation of BMSCs is a core factor in osteoporosis (OP). This study investigates how miR-326 regulates osteogenic differentiation of hBMSCs by targeting NAT10, thereby influencing OP pathogenesis. Method Serum miR-326 levels were measured using RT-qPCR. Its diagnostic value for OP was assessed by ROC analysis, and its correlation with bone mineral density (BMD) was examined. Using a dexamethasone (DEX)-induced hBMSC OP model, we evaluated the effects of miR-326 on osteogenesis (RT-qPCR), cell viability (CCK-8 assay), and inflammation (ELISA). The miR-326–NAT10 interaction was confirmed by dual-luciferase assay. A rescue experiment with co-transfection verified their functional relationship. Results MiR-326 levels in OP patient serum were significantly decreased, and the area under the ROC curve demonstrated excellent diagnostic performance The OP group exhibited significantly lower BMD, which was positively correlated with reduced miR-326 expression. In DEX-induced hBMSCs, miR-326 overexpression promoted osteogenesis by upregulating key markers, enhanced cell viability, and attenuated inflammation. Dual-luciferase assays confirmed NAT10 as a direct target of miR-326. NAT10 was upregulated in OP patients and negatively correlated with miR-326, and oe-NAT10 rescued the pro-osteogenic and anti-inflammatory effects of miR-326. Conclusions miR-326 is downregulated in the OP and can serve as a potential diagnostic biomarker for OP. miR-326 promotes osteogenic differentiation of hBMSCs and inhibits inflammatory responses by targeting NAT10, exerting a protective role in the pathogenesis of OP.