Department of Medical Genetics, Peking University School of Basic Medical Sciences, 100191, Beijing, China.
Peking University Center for Human Disease Genomics, 100191, Beijing, China.
Cell Death Dis. 2019 Feb 20;10(3):172. doi: 10.1038/s41419-019-1428-1.
MicroRNAs (miRs) play an essential role in the regulation of bone formation and homeostasis. miR-185 has been reported to negatively regulate osteogenesis in vitro. However, whether it has an impact on in vivo bone homeostasis remains unknown. Here, we demonstrated that primary osteoblasts and mesenchymal stem cells derived from miR-185-knockout (KO) mice exhibited enhanced osteogenesis. Further, we constructed an ovariectomized mouse model to investigate the role of miR-185 during osteoporosis. Micro-computed tomography revealed an increased bone volume in KO compared to wild-type mice 6 weeks after surgery, indicating redundant bone formation after miR-185 depletion. Dual-luciferase reporter assays identified biglycan (Bgn), which promotes bone formation through the BMP/Smad pathway, as the direct target of miR-185. Taken together, these findings indicate that blocking miR-185 expression increases bone formation during osteoporosis, which may partly occur through the regulation of Bgn expression and BMP/Smad signaling.
微小 RNA（miRs）在骨形成和稳态的调节中发挥着重要作用。已经有报道表明 miR-185 在体外可负向调控成骨作用。然而，其是否对体内骨稳态有影响仍不清楚。在这里，我们证明了 miR-185 敲除（KO）小鼠的原代成骨细胞和间充质干细胞表现出增强的成骨作用。此外，我们构建了去卵巢小鼠模型以研究 miR-185 在骨质疏松症中的作用。Micro-CT 显示术后 6 周 KO 组比野生型小鼠的骨体积增加，表明 miR-185 耗竭后有多余的骨形成。双荧光素酶报告基因检测鉴定出骨连接蛋白（Bgn）是 miR-185 的直接靶标，Bgn 通过 BMP/Smad 通路促进骨形成。总之，这些发现表明阻断 miR-185 的表达可增加骨质疏松症期间的骨形成，这可能部分通过调节 Bgn 表达和 BMP/Smad 信号通路发生。
