Department of Orthopedic Surgery, The People's Hospital of Yuxi City, The 6th Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China.
Health Screening Center, The People's Hospital of Yuxi City, The 6th Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China.
J Cell Physiol. 2018 Sep;233(9):6798-6806. doi: 10.1002/jcp.26430. Epub 2018 Apr 16.
Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p play an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation.
分泌卷曲相关蛋白 1（SFRP1）是 WNT 信号通路的负调控分子，是骨质疏松症中成骨的治疗靶点。本研究首先建立了去卵巢（OVX）大鼠模型来模拟绝经后骨质疏松症，通过 RNA 测序和 qRT-PCR 发现 miR-542-3p 和 sFRP1 表达发生显著变化。此外，绝经后骨质疏松症患者 miR-542-3p 和 sFRP1 mRNA 水平之间存在显著负相关。通过荧光素酶报告基因检测发现 miR-542-3p 抑制 sFRP1 mRNA 的表达。当 sFRP1 3'UTR 中的 miR-542-3p 结合位点缺失时，并不影响其表达。Western blot 结果显示 miR-542-3p 抑制 SFRP1 蛋白的表达。在成骨诱导的间充质干细胞（MSC）中 SFRP1 的表达显著增加，而 miR-542-3p 的表达显著降低。转染 miR-542-3p 的 MSC 中骨特异性标志物的表达明显增加，表明 miR-542-3p 是 MSC 分化所必需的。抑制 miR-542-3p 减少骨形成，证实 miR-542-3p 在体内发挥促进骨形成的作用。总之，这些数据表明 miR-542-3p 通过抑制 SFRP1 表达和诱导成骨细胞分化在骨形成中发挥重要作用。
