NF‐κB p50 and p52 Expression Is Not Required for RANK‐Expressing Osteoclast Progenitor Formation but Is Essential for RANK‐ and Cytokine‐Mediated Osteoclastogenesis

Expression of RANKL by stromal cells and of RANK and both NF‐κB p50 and p52 by osteoclast precursors is essential for osteoclast formation. To examine further the role of RANKL, RANK, and NF‐κB signaling in this process, we used NF‐κB p50−/−;p52−/− double knockout (dKO) and wild‐type (WT) mice. Oste...

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Bibliographic Details
Published in:Journal of bone and mineral research 2002-07, Vol.17 (7), p.1200-1210
Main Authors: Xing, Lianping, Bushnell, Timothy P., Carlson, Louise, Tai, Zhenxing, Tondravi, Mehrdad, Siebenlist, Ulrich, Young, Fay, Boyce, Brendan F.
Format: Article
Language:English
Subjects:
NF‐κB
osteoclast
RANK
RANKL
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Summary:Expression of RANKL by stromal cells and of RANK and both NF‐κB p50 and p52 by osteoclast precursors is essential for osteoclast formation. To examine further the role of RANKL, RANK, and NF‐κB signaling in this process, we used NF‐κB p50−/−;p52−/− double knockout (dKO) and wild‐type (WT) mice. Osteoclasts formed in cocultures of WT osteoblasts with splenocytes from WT mice but not from dKO mice, a finding unchanged by addition of RANKL and macrophage colony‐stimulating factor (M‐CSF). NF‐κB dKO splenocytes formed more colony‐forming unit granulocyte macrophage (CFU‐GM) colonies than WT cells, but no osteoclasts were formed from dKO CFU‐GM colonies. RANKL increased the number of CFU‐GM colonies twofold in WT cultures but not in dKO cultures. Fluorescence‐activated cell sorting (FACS) analysis of splenocytes from NF‐κB dKO mice revealed a two‐to threefold increase in the percentage of CD11b (Mac‐1) and RANK double‐positive cells compared with WT controls. Treatment of NF‐κB dKO splenocytes with interleukin (IL)‐1, TNF‐α, M‐CSF, GM‐CSF, and IL‐6 plus soluble IL‐6 receptor did not rescue the osteoclast defect. No increase in apoptosis was observed in cells of the osteoclast lineage in NF‐κB dKO or p50−/−;p52+/− (3/4KO) mice. Thus, NF‐κB p50 and p52 expression is not required for formation of RANK‐expressing osteoclast progenitors but is essential for RANK‐expressing osteoclast precursors to differentiate into TRAP+ osteoclasts in response to RANKL and other osteoclastogenic cytokines.
ISSN:0884-0431
1523-4681
DOI:10.1359/jbmr.2002.17.7.1200