PMID- 15722361
OWN - NLM
STAT- MEDLINE
DCOM- 20050623
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 16
DP  - 2005 Apr 22
TI  - MCP-1 is induced by receptor activator of nuclear factor-kappaB ligand, 
      promotes human osteoclast fusion, and rescues granulocyte macrophage 
      colony-stimulating factor suppression of osteoclast formation.
PG  - 16163-9
AB  - Human osteoclast formation from monocyte precursors under the action of receptor 
      activator of nuclear factor-kappaB ligand (RANKL) was suppressed by granulocyte 
      macrophage colony-stimulating factor (GM-CSF), with down-regulation of critical 
      osteoclast-related nuclear factors. GM-CSF in the presence of RANKL and 
      macrophage colony-stimulating factor resulted in mononuclear cells that were 
      negative for tartrate-resistant acid phosphatase (TRAP) and negative for bone 
      resorption. CD1a, a dendritic cell marker, was expressed in GM-CSF, RANKL, and 
      macrophage colony-stimulating factor-treated cells and absent in osteoclasts. 
      Microarray showed that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), 
      was profoundly repressed by GM-CSF. Addition of MCP-1 reversed GM-CSF suppression 
      of osteoclast formation, recovering the bone resorption phenotype. MCP-1 and 
      chemokine RANTES (regulated on activation normal T cell expressed and secreted) 
      permitted formation of TRAP-positive multinuclear cells in the absence of RANKL. 
      However, these cells were negative for bone resorption. In the presence of RANKL, 
      MCP-1 significantly increased the number of TRAP-positive multinuclear 
      bone-resorbing osteoclasts (p = 0.008). When RANKL signaling through NFATc1 was 
      blocked with cyclosporin A, both MCP-1 and RANTES expression was down-regulated. 
      Furthermore, addition of MCP-1 and RANTES reversed the effects of cyclosporin A 
      and recovered the TRAP-positive multinuclear cell phenotype. Our model suggests 
      that RANKL-induced chemokines are involved in osteoclast differentiation at the 
      stage of multinucleation of osteoclast precursors and provides a rationale for 
      increased osteoclast activity in inflammatory conditions where chemokines are 
      abundant.
FAU - Kim, Michael S
AU  - Kim MS
AD  - School of Medical Science, Griffith University Gold Coast Campus, Queensland 
      4215, Australia.
FAU - Day, Christopher J
AU  - Day CJ
FAU - Morrison, Nigel A
AU  - Morrison NA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050217
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCL2 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (NFATC1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (TNFRSF11A protein, human)
RN  - 0 (TNFSF11 protein, human)
RN  - 0 (Transcription Factors)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Fusion
MH  - Chemokine CCL2/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Dosage
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*metabolism
MH  - Humans
MH  - Membrane Glycoproteins/*metabolism
MH  - Monocytes/cytology/metabolism
MH  - NFATC Transcription Factors
MH  - Nuclear Proteins/metabolism
MH  - Osteoclasts/cytology/*metabolism
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Transcription Factors/metabolism
EDAT- 2005/02/22 09:00
MHDA- 2005/06/24 09:00
CRDT- 2005/02/22 09:00
PHST- 2005/02/22 09:00 [pubmed]
PHST- 2005/06/24 09:00 [medline]
PHST- 2005/02/22 09:00 [entrez]
AID - S0021-9258(20)69296-1 [pii]
AID - 10.1074/jbc.M412713200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Apr 22;280(16):16163-9. doi: 10.1074/jbc.M412713200. Epub 2005 
      Feb 17.