Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):949-957. doi: 10.26355/eurrev_201902_16981.
This study aims to investigate whether circ-VANGL1 can promote the progression of osteoporosis (OP) by absorbing miRNA-217 to regulate RUNX2 expression.
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.
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.
Circ-VANGL1 promotes the development of OP via binding to miRNA-217 to downregulate RUNX2 expression.
本研究旨在探讨环状 RNA 血管生成素样 1（circ-VANGL1）是否通过吸收 miRNA-217 来调节 runt 相关转录因子 2（RUNX2）的表达，从而促进骨质疏松症（OP）的进展。
采用实时定量聚合酶链反应（qRT-PCR）检测 OP 患者和非 OP 患者血清中 circ-VANGL1、miRNA-217 和 RUNX2 的水平，并检测不同成骨分化时间点人骨髓间充质干细胞（hBMSCs）中它们的表达水平。Western blot 检测 hBMSCs 中 RUNX2 和成骨蛋白（BSP、OCN、OPN）的表达水平。双荧光素酶报告基因实验验证 circ-VANGL1、miRNA-217 和 RUNX2 之间的关系。碱性磷酸酶（ALP）染色评估 circ-VANGL1 和 miRNA-217 对成骨分化程度的影响。
OP 患者血清中 miRNA-217 水平升高，circ-VANGL1 水平降低，RUNX2 水平降低。circ-VANGL1 通过吸收 miRNA-217 调节 RUNX2 表达，加速成骨分化。此外，miRNA-217 通过靶向 RUNX2 3'UTR 降解 RUNX2 抑制成骨分化。circ-VANGL1 的过表达上调 RUNX2、BSP、OCN 和 OPN 的表达。同时，hBMSCs 中转录物 circ-VANGL1 过表达后 ALP 活性增加。然而，circ-VANGL1 与 miRNA-217 的共过表达并没有改变 RUNX2 的表达。hBMSCs 中转录物 circ-VANGL1 与 miRNA-217 共过表达后 ALP 活性略有增加，但与对照组无差异。
circ-VANGL1 通过与 miRNA-217 结合下调 RUNX2 表达，促进 OP 的发展。
