抑制 miR-451a 通过 Bmp6 信号通路在骨质疏松症中加速成骨分化并抑制骨丢失。

Suppression of miR-451a accelerates osteogenic differentiation and inhibits bone loss via Bmp6 signaling during osteoporosis.

机构信息

Department of Orthopedics, The Second Hospital of Shan Xi Medical University, Taiyuan City, Shanxi Province, 030001, China.

Department of Orthopedics Dept. Unit 6, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China.

出版信息

Biomed Pharmacother. 2019 Dec;120:109378. doi: 10.1016/j.biopha.2019.109378. Epub 2019 Sep 18.

DOI:10.1016/j.biopha.2019.109378

PMID:31541885

Abstract

Bone homeostasis is known as a dynamic balance, including bone formation through osteoblasts and bone resorption by osteoclasts. MicroRNAs (miRs) play a critical role in regulating bone formation and homeostasis. In the study, the effects of miR-451a on bone homeostasis were investigated. The results indicated that the primary osteoblasts and mesenchymal stem cells (MSCs), as the main source of osteoblasts, isolated from miR-451a-knockout (KO) mice showed promoted osteogenesis. in vivo, an ovariectomized (OVX) animal model was used to further explore the effect of miR-451a on osteoporosis. Micro-computed tomography (μCT) indicated a promoted bone volume in miR-451a-KO mice compared to wild-type (WT) mice after OVX operation, demonstrating a redundant bone formation after the knockout of miR-451a. Importantly, we for the first time found that bone morphogenetic protein 6 (Bmp6) was a direct target of miR-451a, elevating bone formation through regulating SMAD1/5/8 expression. In conclusion, reducing miR-451a expression levels could enhance bone formation during the progression of osteoporosis, which might be at least partly via the meditation of Bmp6 expression.

摘要

骨稳态被认为是一种动态平衡，包括成骨细胞介导的骨形成和破骨细胞介导的骨吸收。微小 RNA（miRs）在调节骨形成和稳态中起着关键作用。在这项研究中，研究了 miR-451a 对骨稳态的影响。结果表明，从 miR-451a 敲除（KO）小鼠中分离的原代成骨细胞和成骨细胞间充质干细胞（MSCs）作为成骨细胞的主要来源，表现出促进成骨作用。在体内，使用去卵巢（OVX）动物模型进一步探讨了 miR-451a 对骨质疏松症的影响。微计算机断层扫描（μCT）表明，与野生型（WT）小鼠相比，OVX 手术后 miR-451a-KO 小鼠的骨体积增加，表明 miR-451a 敲除后骨形成过剩。重要的是，我们首次发现骨形成蛋白 6（Bmp6）是 miR-451a 的直接靶标，通过调节 SMAD1/5/8 的表达来促进骨形成。总之，降低 miR-451a 的表达水平可以增强骨质疏松症进展过程中的骨形成，这可能至少部分是通过 Bmp6 表达的调节。