Circ-VANGL1 promotes the progression of osteoporosis by absorbing miRNA-217 to regulate RUNX2 expression

L. Yang, Z. Zeng, N. Kang, J.-C. Yang, X. Wei, Y. Hai

Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. prof.haiyong@yahoo.com

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• Orthopedics

OBJECTIVE: This study aims to investigate whether circ-VANGL1 can promote the progression of osteoporosis (OP) by absorbing miRNA-217 to regulate RUNX2 expression.

PATIENTS AND METHODS: The serum levels of circ-VANGL1, miRNA-217 and RUNX2 in OP patients and non-OP patients were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Their expression levels in human bone marrow mesenchymal stem cells (hBMSCs) at different time points of osteogenesis differentiation were determined as well. The expression levels of RUNX2 and osteogenic proteins (BSP, OCN, OPN) in hBMSCs were detected by Western blot. Dual-Luciferase reporter gene assay was performed to verify the relationship among circ-VANGL1, miRNA-217 and RUNX2. Alkaline phosphatase (ALP) staining was conducted to evaluate the degree of osteogenic differentiation influenced by circ-VANGL1 and miRNA-217.

RESULTS: OP patients presented a higher serum level of miRNA-217 and lower serum levels of circ-VANGL1 and RUNX2 relative to non-OP patients. Circ-VANGL1 accelerated osteogenic differentiation by absorbing miRNA-217 to regulate RUNX2 expression. Moreover, miRNA-217 inhibited osteogenic differentiation by degrading RUNX2 by targeting to RUNX2 3’UTR. The overexpression of circ-VANGL1 upregulated expressions of RUNX2, BSP, OCN, and OPN. Meanwhile, ALP activity increased in hBMSCs overexpressing circ-VANGL1. However, co-overexpression of circ-VANGL1 and miRNA-217 did not alter RUNX2 expression. ALP activity in hBMSCs co-overexpressing circ-VANGL1 and miRNA-217 slightly increased, but had no difference with controls.

CONCLUSIONS: Circ-VANGL1 promotes the development of OP via binding to miRNA-217 to downregulate RUNX2 expression.

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