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

Cell Death & Disease
Qi CuiHongshan Zhao

Abstract

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.

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Citations

Jul 10, 2019·International Journal of Molecular Sciences·Po-Chun ChenChih-Hsin Tang
Jan 18, 2020·Journal of Cellular Physiology·Guan-Zhi LiuPei Yang
Aug 28, 2020·International Journal of Molecular Sciences·Yongguang GaoAirong Qian
Oct 17, 2019·International Journal of Molecular Sciences·Francesca BalzanoMargherita Maioli
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Erick BreathwaiteJung Bok Lee
Jul 16, 2020·International Journal of Molecular Sciences·Yu-Shan ChenFeng-Sheng Wang
Dec 2, 2020·International Journal of Molecular Sciences·Massimo De MartinisSebastiano Gangemi
Jan 4, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yu Seon Kim, Antonios G Mikos
Nov 22, 2020·Bone·Austin P Hensley, Audrey McAlinden
Dec 24, 2019·Trends in Cell Biology·Bing-Dong SuiCheng-Hu Hu
Mar 12, 2021·Biochemical and Biophysical Research Communications·Bin ZhouYijun Kang
Jun 25, 2021·Frontiers in Cell and Developmental Biology·Chao YangQiang Chen
Jul 27, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Samadian
Dec 23, 2021·Experimental and Therapeutic Medicine·Jianmin GuoJun Zou

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