破骨细胞
兰克尔
下调和上调
STAT1
细胞生物学
节的
细胞分化
化学
生物
癌症研究
信号转导
基因
激活剂(遗传学)
体外
解剖
生物化学
作者
Jung Ha Kim,Kabsun Kim,Inyoung Kim,Semun Seong,Jeong‐Tae Koh,Nacksung Kim
摘要
Abstract Several members of the transforming growth factor beta (TGF‐β) superfamily regulate the proliferation, differentiation, and function of bone‐forming osteoblasts and bone‐resorbing osteoclasts. However, it is still unknown whether Nodal, a member of the TGF‐β superfamily, serves a function in bone cells. In this study, we found that Nodal did not have any function in osteoblasts but instead negatively regulated osteoclast differentiation. Nodal inhibited RANKL‐induced osteoclast differentiation by downregulating the expression of pro‐osteoclastogenic genes, including c‐fos , Nfatc1 , and Blimp1 , and upregulating the expression of antiosteoclastogenic genes, including Bcl6 and Irf8 . Nodal activated STAT1 in osteoclast precursor cells, and STAT1 downregulation significantly reduced the inhibitory effect of Nodal on osteoclast differentiation. These findings indicate that Nodal activates STAT1 to downregulate or upregulate the expression of pro‐osteoclastogenic or antiosteoclastogenic genes, respectively, leading to the inhibition of osteoclast differentiation. Moreover, the inhibitory effect of Nodal on osteoclast differentiation contributed to the reduction of RANKL‐induced bone loss in vivo.
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