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. 2025 Jul 10;162(1):124.
doi: 10.1186/s41065-025-00494-5.

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

Jindong Chen #  1 , Shilong Zhang #  2 , Dixin Cai  3 , Qing Yin  4 , Qian Xie  5 , Pengfang Xu  5 , Junling Zhu  6
Affiliations

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

Jindong Chen et al. Hereditas. .

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.

Keywords: BMSC; Diagnosis; Osteoporosis; Postmenopausal; SDCBP2-AS1; miR-361-3p.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The procedures used in this study adhere to the tenets of the Declaration of Helsinki. All individuals involved in the study were advised of its objectives and provided signed consent forms. The research protocol received ethical clearance from the Ethics Committee at The First Affiliated Hospital of Xiamen University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
lncRNA SDCBP2-AS1 expression in patients with PMOP. (A) Serum SDCBP2-AS1 was downregulated in patients with PMOP compared to controls. (B) There is a positive correlation between SDCBP2-AS1 expression and T scores in patients with PMOP. (C-E). A positive relationship was observed between SDCBP2-AS1 expression and total hip BMD, femoral neck BMD, and L1-4 BMD levels. **P < 0.01
Fig. 2
Fig. 2
The expression and clinical role of SDCBP2-AS1 in PMOP patients with fractures. (A) Serum SDCBP2-AS1 expression was lower in PMOP patients with fractures than in patients without fractures. (B) ROC curve indicated that SDCBP2-AS1 has potential diagnostic value in distinguishing patients with fractures from those without fractures with a relatively high AUC value. (C) SDCBP2-AS1 levels were gradually increased after treatment in patients with fractures. **P < 0.01
Fig. 3
Fig. 3
The effect of SDCBP2-AS1 on osteoblast activity in hBMSCs. (A) The osteogenic differentiation indicators ALP, OCN, RUNX2, and Collagen I mRNA levels increased in osteoblast differentiation. (B) SDCBP2-AS1 expression gradually increased during osteoblast differentiation. (C) RT-qPCR method was utilized to detect the transfection efficiency in hBMSCs. (D) Overexpression of SDCBP2-AS1 promoted cell proliferation, while knockdown of its expression inhibited cell proliferation. (E) Enhanced SDCBP2-AS1 repressed cell apoptosis, while decreased expression of SDCBP2-AS1 promoted cell apoptosis. (F) The levels of ALP, OCN, RUNX2, and Collagen I increased in oe-SDCBP2-AS1 transfected cells, while decreasing in si-SDCBP2-AS1 transfected cells. **P < 0.01
Fig. 4
Fig. 4
miR-361-3p was a direct target miRNA of SDCBP2-AS1. (A) The StarBase database predicted the binding sites between SDCBP2-AS1 and miR-361-3p. (B) Dual-luciferase reporter assay confirmed the binding relationship between SDCBP2-AS1 and miR-361-3p. (C) RIP assay further confirmed both SDCBP2-AS1 and miR-361-3p were enriched on anti-Ago2. (D) Serum miR-361-3p was upregulated in patients with PMOP. (E) A negative correlation between SDCBP2-AS1 and miR-361-3p was observed in patients with PMOP. (F) An increased expression miR-361-3p was observed in patients with fractures. (G) miR-361-3p gradually decreased during osteoblast differentiation. (H) miR-361-3p expression was decreased in oe-SDCBP2-AS1 transfected cells while increased in si-SDCBP2-AS1 transfected cells. *P < 0.05, **P < 0.01
Fig. 5
Fig. 5
miR-361-3p partially reversed the effects of SDCBP2-AS1 on osteoblast activities in hBMSCs. (A) RT-qPCR was utilized to detect the miR-361-3p expression after co-transfection. (B) Overexpression partially reversed the enhanced proliferation abilities caused by oe-SDCBP2-AS1. (C) The inhibited apoptosis by SDCBP2-AS1 was reversed by enhanced miR-361-3p expression. (D) Elevation of osteoblast differentiation-related markers (ALP, OCN, RUNX2, and Collagen I) expression by SDCBP2-AS1 was partially reversed by miR-361-3p overexpression. *P < 0.05
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