Nodal negatively regulates osteoclast differentiation by inducing STAT1 phosphorylation

被引：1

作者：

Kim, Jung Ha ^{[1
,2
]}

Kim, Kabsun ^{[1
]}

Kim, Inyoung ^{[1
]}

Seong, Semun ^{[1
,2
]}

Koh, Jeong-Tae ^{[2
,3
]}

Kim, Nacksung ^{[1
,2
,4
]}

机构：

[1] Chonnam Natl Univ, Med Sch, Dept Pharmacol, Gwangju, South Korea

[2] Chonnam Natl Univ, Hard Tissue Biointerface Res Ctr, Sch Dent, Gwangju, South Korea

[3] Chonnam Natl Univ, Sch Dent, Dept Pharmacol & Dent Therapeut, Gwangju, South Korea

[4] Chonnam Natl Univ, Med Sch, Dept Pharmacol, Gwangju 61469, South Korea

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2024年 / 239卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Nodal; osteoblast; osteoclast; STAT1; TGF-beta; BONE-RESORPTION; TGF-BETA; EXPRESSION; PROMOTES; GROWTH; OSTEOIMMUNOLOGY; MACROPHAGES; PATHWAYS; RECEPTOR; IMMUNE;

D O I：

10.1002/jcp.31268

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Several members of the transforming growth factor beta (TGF-beta) 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-beta 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.

引用

页数：10

共 33 条

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