Mmu-miR-185 depletion promotes osteogenic differentiation and suppresses bone loss in osteoporosis through the Bgn-mediated BMP/Smad pathway

被引：86

作者：

Cui, Qi ^{[1
,2
]}

Xing, Jinhao ^{[1
,2
]}

Yu, Miao ^{[3
,4
,5
]}

Wang, Yue ^{[3
,4
,5
]}

Xu, Jian ^{[6
]}

Gu, Yajuan ^{[1
,2
]}

Nan, Xu ^{[1
,2
]}

Ma, Wenping ^{[1
,2
]}

Liu, Hao ^{[5
,7
,8
,9
]}

Zhao, Hongshan ^{[1
,2
]}

机构：

[1] Peking Univ, Sch Basic Med Sci, Dept Med Genet, Beijing 100191, Peoples R China

[2] Peking Univ, Ctr Human Dis Genom, Beijing 100191, Peoples R China

[3] Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, Beijing 100081, Peoples R China

[4] Natl Clin Res Ctr Oral Dis, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100081, Peoples R China

[5] Beijing Key Lab Digital Stomatol, Beijing 100081, Peoples R China

[6] Peking Univ, Sch Basic Med Sci, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China

[7] Peking Univ, Sch & Hosp Stomatol, Cent Lab, Beijing 100081, Peoples R China

[8] Natl Clin Res Ctr Oral Dis, Beijing 100081, Peoples R China

[9] Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100081, Peoples R China

来源：

CELL DEATH & DISEASE | 2019年 / 10卷 / 3期

基金：

中国国家自然科学基金;

关键词：

OSTEOBLAST DIFFERENTIATION; MICRORNA; GENE; OSTEOCLASTOGENESIS; KINASE;

D O I：

10.1038/s41419-019-1428-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页数：14

共 28 条

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Modulation of canonical Wnt signaling by the extracellular matrix component biglycan [J].