Department of Spinal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Cell Biol Int. 2021 Feb;45(2):447-455. doi: 10.1002/cbin.11502. Epub 2020 Nov 25.
Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment.
越来越多的证据表明，绝经后骨质疏松症（PMO）是一种严重的紊乱，它给绝经后妇女带来了沉重的身体、心理社会和经济负担，并极大地影响了她们的生活质量。环状 RNA（circRNAs）和 microRNA（miRs）在 PMO 的发生和发展中发挥着重要作用。然而，circRNAs 和 miRs 在骨质疏松症调节中的作用仍需进一步研究。通过 RNA-seq 和生物信息学分析筛选出 PMO 患者中表达水平不同的 circRNAs。我们发现 circ_0007059 在 PMO 患者和人骨髓基质细胞（hBMSCs）的破骨细胞分化中上调。接下来，我们研究了 circ_0007059 在 hBMSCs 破骨细胞分化中的过表达效应。circ_0007059 过表达在体外抑制 hBMSC 向破骨细胞分化。这通过下调骨形态发生蛋白 2（BMP-2）的表达、上调破骨细胞特异性基因的表达和 TRAP 染色来证明。通过生物信息学分析和双荧光素酶报告基因检测，证明 circ_0007059 可直接靶向 miR-378，进而通过 miR-378 靶向 BMP-2。转染 miR-378 模拟物可逆转 circ_0007059 对 hBMSCs 破骨细胞分化的影响。这些结果表明，circ_0007059 通过 miR-378/BMP-2 信号通路在破骨细胞分化中发挥重要作用。靶向 circ_0007059/miR-378/BMP-2 轴可能是骨质疏松症治疗的新策略。
