MiR-664-3p suppresses osteoblast differentiation and impairs bone formation via targeting Smad4 and Osterix.
MiR-664-3p suppresses osteoblast differentiation and impairs bone formation via targeting Smad4 and Osterix.
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MiR-664-3p 通过靶向 Smad4 和 Osterix 抑制成骨细胞分化并损害骨形成
DOI：
10.1111/jcmm.16451
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发表时间：
2021-06
影响因子：
5.3
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Xu Y;Jin Y;Hong F;Ma Y;Yang J;Tang Y;Zhu Z;Wu J;Bao Q;Li L;Yao B;Li D;Ma C
骨质疏松症是一种代谢紊乱疾病，其特征为骨量低和微结构退化，骨折风险增加。一些微小核糖核酸（miRNAs）已被证实是成骨细胞分化的潜在调节因子，可维持骨量。我们的微小核糖核酸测序结果显示，在成骨前体细胞MC3T3 - E1的成骨分化过程中，miR - 664 - 3p显著下调。然而，miR - 664 - 3p是否对骨稳态有影响仍不清楚。在本研究中，我们发现miR - 664 - 3p的过表达在体外抑制了成骨细胞活性和基质矿化。成骨细胞中miR - 664 - 3p转基因小鼠由于成骨细胞功能受抑制而表现出骨量减少。靶点预测分析和实验验证证实Smad4和Osterix（Osx）是miR - 664 - 3p的直接靶点。此外，通过骨膜下注射miR - 664 - 3p拮抗剂对miR - 664 - 3p进行特异性抑制可防止卵巢切除诱导的骨质流失。另外，与正常受试者相比，骨质疏松症患者血清中miR - 664 - 3p的表达明显更高。综上所述，本研究揭示miR - 664 - 3p通过靶向Smad4和Osx抑制骨生成和骨形成。这也凸显了miR - 664 - 3p作为骨质疏松症患者一种新的诊断和治疗靶点的潜力。
Osteoporosis is a metabolic disorder characterized by low bone mass and deteriorated microarchitecture, with an increased risk of fracture. Some miRNAs have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass. Our miRNA sequencing results showed that miR‐664‐3p was significantly down‐regulated during the osteogenic differentiation of the preosteoblast MC3T3‐E1 cells. However, whether miR‐664‐3p has an impact on bone homeostasis remains unknown. In this study, we identified overexpression of miR‐664‐3p inhibited the osteoblast activity and matrix mineralization in vitro. Osteoblastic miR‐664‐3p transgenic mice exhibited reduced bone mass due to suppressed osteoblast function. Target prediction analysis and experimental validation confirmed Smad4 and Osterix (Osx) are the direct targets of miR‐664‐3p. Furthermore, specific inhibition of miR‐664‐3p by subperiosteal injection with miR‐664‐3p antagomir protected against ovariectomy‐induced bone loss. In addition, miR‐664‐3p expression was markedly higher in the serum from patients with osteoporosis compared to that from normal subjects. Taken together, this study revealed that miR‐664‐3p suppressed osteogenesis and bone formation via targeting Smad4 and Osx. It also highlights the potential of miR‐664‐3p as a novel diagnostic and therapeutic target for osteoporotic patients.
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影响因子：
4.6
作者：
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通讯作者：
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通讯作者：
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