Quercetin promotes osteogenic differentiation of bone marrow mesenchymal stem cells by modulating the miR-214-3p/Wnt3a/β-catenin signaling pathway

Abstract

Postmenopausal osteoporosis, primarily driven by estrogen deficiency, is predominantly mediated through estrogen receptors such as ERα. However, the underlying mechanisms necessitate further investigation. In this study, we established an ERα-deficient model in rBMSCs to elucidate the role of ERα in osteogenic differentiation and miRNA expression profiles. Our findings demonstrate that knockdown of ERα inhibits osteogenic differentiation in rBMSCs, resulting in upregulation of 25 miRNAs and downregulation of 184 miRNAs, including a significant increase in the expression of miR-214-3p. Validation using qPCR, Western blotting, and bioinformatics analysis revealed that miR-214-3p negatively regulates osteogenic differentiation via the Wnt/β-catenin signaling pathway. Furthermore, we explored the potential therapeutic effects of quercetin (QUE) on rBMSCs. CCK8, alkaline phosphatase activity assays, and Alizarin Red staining demonstrated that QUE dose-dependently enhances rBMSCs proliferation, alkaline phosphatase activity, and mineralization within the concentration range of 0.1–1 μM. Importantly, QUE was found to downregulate miR-214-3p expression and activate the Wnt3a/β-catenin signaling pathway. Rescue experiments confirmed that QUE could counteract the inhibitory effects of miR-214-3p on the Wnt3a/β-catenin signaling pathway. Collectively, our study provides compelling evidence that knockdown of ERα inhibits the osteogenic differentiation of rBMSCs by affecting the miRNA expression profile, while QUE can reverse the inhibitory effect exerted by miR-214-3p on the Wnt3a/β-catenin signaling pathway, thereby offering novel insights into diagnosis, prevention, and treatment strategies for postmenopausal osteoporosis.