LncRNA SDCBP2-AS1 is a putative biomarker for postmenopausal osteoporosis and promotes osteogenic differentiation of BMSCs by regulating miR-361-3p

lncRNA SDCBP2-AS1 是绝经后骨质疏松症的潜在生物标志物,它通过调控 miR-361-3p 促进骨髓间充质干细胞的成骨分化。

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Abstract

BACKGROUND: Numerous long noncoding RNAs (lncRNAs) have been proven to participate in osteogenesis and postmenopausal osteoporosis (PMOP). We measured serum SDCBP2-AS1 expression changes in patients with PMOP and investigated its effects on osteoblast differentiation in human bone marrow-derived mesenchymal stem cells (hBMSC) cells. METHODS: RT-qPCR was used to measure SDCBP2-AS1 levels and the expression of osteogenic differentiation indicators. The diagnostic efficacy of SDCBP2-AS1 was assessed using a receiver operating characteristic (ROC) analysis. CCK-8 and flow cytometry methods were employed to investigate the functional impact of SDCBP2-AS1 on hBMSC cell proliferation and apoptosis during osteoblast differentiation. The bioinformatics, dual-luciferase reporter assay, and RNA Immunoprecipitation (RIP) assay were used to identify and confirm SDCBP2-AS1/miR-361-3p interaction. RESULTS: Serum SDCBP2-AS1 was decreased in patients with PMOP, especially in those with fractures. The SDCBP2-AS1 levels were positively correlated with patients' T scores and BMDs. Decreased SDCBP2-AS1 had a certain high area under the ROC curve (AUC) value (AUC = 0.81) in distinguishing PMOP patients with fractures from those without fractures. SDCBP2-AS1 levels gradually increased after four weeks of treatment in PMOP patients and hBMSCs during cell differentiation. Enhanced SDCBP2-AS1 promoted cell proliferation and the levels of osteoblast differentiation markers, including ALP, OCN, RUNX2, and Collagen I, while decreasing cell apoptosis. miR-361-3p was a direct target of SDCBP2-AS1. The influence of SDCBP2-AS1 on cell activities and hBMSCs differentiation was diminished by miR-361-3p. CONCLUSIONS: SDCBP2-AS1 might be a diagnostic biomarker in predicting PMOP patients with fractures. By measuring the levels of SDCBP2-AS1 in patient samples, clinicians may be able to identify those who are more susceptible to bone fractures, enabling earlier and more targeted preventive measures. SDCBP2-AS1 targeting miR-361-3p regulates the osteogenic differentiation of hBMSCs, which might be a new target for the treatment of PMOP.

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