NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1

Teruhito Yamashita, Zhenqiang Yao, Fang Li, Qian Zhang, I. Raul Badell, Edward M. Schwarz, Sunao Takeshita, Erwin F. Wagner, Masaki Noda, Koichi Matsuo, Lianping Xing, Brendan F. Boyce

Research output: Contribution to journalArticle

236 Citations (Scopus)

Abstract

Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor (TNF). Osteoclast formation induced by these cytokines requires NF-κB p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors. c-Fos induces NFATc1, but the relationship between NF-κB and these other transcription factors in osteoclastogenesis remains poorly understood. We report that RANKL and TNF can induce osteoclast formation directly from NF-κB p50/p52 double knockout (dKO) osteoclast precursors when either c-Fos or NFATc1 is expressed. RANKL- or TNF-induced c-Fos up-regulation and activation are abolished in dKO cells and in wild-type cells treated with an NF-κB inhibitor. c-Fos expression requires concomitant RANKL or TNF treatment to induce NFATc1 activation in the dKO cells. Furthermore, c-Fos expression increases the number and resorptive capacity of wild-type osteoclasts induced byTNF in vitro.Weconclude that NF-κB controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1. Inhibition of NF-κB should prevent RANKL- and TNF-induced bone resorption.

Original languageEnglish
Pages (from-to)18245-18253
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
Publication statusPublished - 2007 Jun 22

Fingerprint

Osteoclasts
Tumor Necrosis Factor-alpha
Ligands
Chemical activation
Bone Resorption
Bone
Postmenopausal Osteoporosis
Osteogenesis
Transcription Factors
Up-Regulation
Joints
Cytokines

ASJC Scopus subject areas

  • Biochemistry

Cite this

NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1. / Yamashita, Teruhito; Yao, Zhenqiang; Li, Fang; Zhang, Qian; Badell, I. Raul; Schwarz, Edward M.; Takeshita, Sunao; Wagner, Erwin F.; Noda, Masaki; Matsuo, Koichi; Xing, Lianping; Boyce, Brendan F.

In: Journal of Biological Chemistry, Vol. 282, No. 25, 22.06.2007, p. 18245-18253.

Research output: Contribution to journalArticle

Yamashita, Teruhito ; Yao, Zhenqiang ; Li, Fang ; Zhang, Qian ; Badell, I. Raul ; Schwarz, Edward M. ; Takeshita, Sunao ; Wagner, Erwin F. ; Noda, Masaki ; Matsuo, Koichi ; Xing, Lianping ; Boyce, Brendan F. / NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 25. pp. 18245-18253.
@article{996aa8d545e24b02b0b82a188807b562,
title = "NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1",
abstract = "Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor (TNF). Osteoclast formation induced by these cytokines requires NF-κB p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors. c-Fos induces NFATc1, but the relationship between NF-κB and these other transcription factors in osteoclastogenesis remains poorly understood. We report that RANKL and TNF can induce osteoclast formation directly from NF-κB p50/p52 double knockout (dKO) osteoclast precursors when either c-Fos or NFATc1 is expressed. RANKL- or TNF-induced c-Fos up-regulation and activation are abolished in dKO cells and in wild-type cells treated with an NF-κB inhibitor. c-Fos expression requires concomitant RANKL or TNF treatment to induce NFATc1 activation in the dKO cells. Furthermore, c-Fos expression increases the number and resorptive capacity of wild-type osteoclasts induced byTNF in vitro.Weconclude that NF-κB controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1. Inhibition of NF-κB should prevent RANKL- and TNF-induced bone resorption.",
author = "Teruhito Yamashita and Zhenqiang Yao and Fang Li and Qian Zhang and Badell, {I. Raul} and Schwarz, {Edward M.} and Sunao Takeshita and Wagner, {Erwin F.} and Masaki Noda and Koichi Matsuo and Lianping Xing and Boyce, {Brendan F.}",
year = "2007",
month = "6",
day = "22",
doi = "10.1074/jbc.M610701200",
language = "English",
volume = "282",
pages = "18245--18253",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "25",

}

TY - JOUR

T1 - NF-κB p50 and p52 regulate receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1

AU - Yamashita, Teruhito

AU - Yao, Zhenqiang

AU - Li, Fang

AU - Zhang, Qian

AU - Badell, I. Raul

AU - Schwarz, Edward M.

AU - Takeshita, Sunao

AU - Wagner, Erwin F.

AU - Noda, Masaki

AU - Matsuo, Koichi

AU - Xing, Lianping

AU - Boyce, Brendan F.

PY - 2007/6/22

Y1 - 2007/6/22

N2 - Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor (TNF). Osteoclast formation induced by these cytokines requires NF-κB p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors. c-Fos induces NFATc1, but the relationship between NF-κB and these other transcription factors in osteoclastogenesis remains poorly understood. We report that RANKL and TNF can induce osteoclast formation directly from NF-κB p50/p52 double knockout (dKO) osteoclast precursors when either c-Fos or NFATc1 is expressed. RANKL- or TNF-induced c-Fos up-regulation and activation are abolished in dKO cells and in wild-type cells treated with an NF-κB inhibitor. c-Fos expression requires concomitant RANKL or TNF treatment to induce NFATc1 activation in the dKO cells. Furthermore, c-Fos expression increases the number and resorptive capacity of wild-type osteoclasts induced byTNF in vitro.Weconclude that NF-κB controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1. Inhibition of NF-κB should prevent RANKL- and TNF-induced bone resorption.

AB - Postmenopausal osteoporosis and rheumatoid joint destruction result from increased osteoclast formation and bone resorption induced by receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor (TNF). Osteoclast formation induced by these cytokines requires NF-κB p50 and p52, c-Fos, and NFATc1 expression in osteoclast precursors. c-Fos induces NFATc1, but the relationship between NF-κB and these other transcription factors in osteoclastogenesis remains poorly understood. We report that RANKL and TNF can induce osteoclast formation directly from NF-κB p50/p52 double knockout (dKO) osteoclast precursors when either c-Fos or NFATc1 is expressed. RANKL- or TNF-induced c-Fos up-regulation and activation are abolished in dKO cells and in wild-type cells treated with an NF-κB inhibitor. c-Fos expression requires concomitant RANKL or TNF treatment to induce NFATc1 activation in the dKO cells. Furthermore, c-Fos expression increases the number and resorptive capacity of wild-type osteoclasts induced byTNF in vitro.Weconclude that NF-κB controls early osteoclast differentiation from precursors induced directly by RANKL and TNF, leading to activation of c-Fos followed by NFATc1. Inhibition of NF-κB should prevent RANKL- and TNF-induced bone resorption.

UR - http://www.scopus.com/inward/record.url?scp=34547124586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547124586&partnerID=8YFLogxK

U2 - 10.1074/jbc.M610701200

DO - 10.1074/jbc.M610701200

M3 - Article

VL - 282

SP - 18245

EP - 18253

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 25

ER -