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 language | English |
|---|---|
| Pages (from-to) | 18245-18253 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - 2007 Jun 22 |
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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 journal › Article
}
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.
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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 -