miR-146a-5p targets Sirt1 to regulate bone mass

Autor: Mingxia Zheng, Junlong Tan, Xiangning Liu, Fujun Jin, Renfa Lai, Xiaogang Wang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Bone Reports, Vol 14, Iss , Pp 101013- (2021)
Druh dokumentu: article
ISSN: 2352-1872
DOI: 10.1016/j.bonr.2021.101013
Popis: MicroRNAs (miRNAs) have been proven to serve as key post-transcriptional regulators, affecting diverse biological processes including osteogenic differentiation and bone formation. Recently, it has been reported that miR-146a-5p affects the activity of both osteoblasts and osteoclasts. However, the target genes of miR-146a-5p in these procedures remain unknown. Here we identify miR-146a-5p as a critical suppressor of osteoblastogenesis and bone formation. We found that miR-146a-5p knockout mice exhibit elevated bone formation and enhanced bone mass in vivo. Consistently, we also found that miR-146a-5p inhibited the osteoblast differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Importantly, we further demonstrated that miR-146a-5p directly targeted Sirt1 to inhibit osteoblast activity. Additionally, we showed that the expression of miR-146a-5p gradually increased in femurs with age not only in female mice but also in female patients, and miR-146a-5p deletion protected female mice from age-induced bone loss. These data suggested that miR-146a-5p has a crucial role in suppressing the bone formation and that inhibition of miR-146a-5p may be a strategy for ameliorating osteoporosis.
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