间充质干细胞
条件基因敲除
骨髓
细胞生物学
甲状旁腺激素
表观遗传学
生物
脂肪生成
癌症研究
干细胞
医学
内科学
免疫学
钙
表型
遗传学
基因
作者
Yaxu Wu,Liang Xie,Mengyuan Wang,Qing Xiong,Yuchen Guo,Liang Yu,Jing Li,Rui Sheng,Peng Deng,Yuan Wang,Rixin Zheng,Yi‐Zhou Jiang,Ling Ye,Qianming Chen,Xuedong Zhou,Shuibin Lin,Quan Yuan
标识
DOI:10.1038/s41467-018-06898-4
摘要
Abstract N 6 -methyladenosine (m 6 A) is the most abundant epigenetic modification in eukaryotic mRNAs and is essential for multiple RNA processing events during mammalian development and disease control. Here we show that conditional knockout of the m 6 A methyltransferase Mettl3 in bone marrow mesenchymal stem cells (MSCs) induces pathological features of osteoporosis in mice. Mettl3 loss-of-function results in impaired bone formation, incompetent osteogenic differentiation potential and increased marrow adiposity. Moreover, Mettl3 overexpression in MSCs protects the mice from estrogen deficiency-induced osteoporosis. Mechanistically, we identify PTH (parathyroid hormone)/Pth1r (parathyroid hormone receptor-1) signaling axis as an important downstream pathway for m 6 A regulation in MSCs. Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Pth1r, and disrupts the PTH-induced osteogenic and adipogenic responses in vivo. Our results demonstrate the pathological outcomes of m 6 A mis-regulation in MSCs and unveil novel epitranscriptomic mechanism in skeletal health and diseases.
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