破骨细胞
基因敲除
组织蛋白酶K
奶油
基因沉默
下调和上调
内科学
化学
细胞生物学
促卵泡激素
内分泌学
兰克尔
癌症研究
生物
激活剂(遗传学)
激素
医学
转录因子
生物化学
受体
细胞凋亡
促黄体激素
基因
作者
Xiaosa Li,Chao Fan,Jiale Wang,Ping Li,Xingyan Xu,Ruixin Guo,Jinzhi Wei,Yang Cheng,Hui‐Ping Lin,Xiaodong Fu
摘要
Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts via stimulating methyltransferase-like 3 (METTL3) protein expression. FSH enhanced osteoclast migration, while the knockdown of METTL3 eliminated this enhancement. Both MeRIP-seq and RNA sequencing identified that cathepsin K (CTSK) is the potential downstream target of METTL3. Knockdown of CTSK reduced FSH-upregulated osteoclast migration. Furthermore, silencing METTL3 decreased CTSK mRNA stability. Finally, FSH induced phosphorylation of cyclic-AMP response element-binding protein (CREB), while silencing of CREB attenuated the effects of FSH on the promoter transcriptional activity of Mettl3 and CTSK/METTL3 protein. Taken together, these findings indicate that FSH promotes osteoclast migration via the CREB/METTL3/CTSK signaling pathway, which may provide a potential target for suppressing osteoclast mobility and postmenopausal osteoporosis therapy.
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