PMID- 14505357
OWN - NLM
STAT- MEDLINE
DCOM- 20040527
LR  - 20131121
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 90
IP  - 2
DP  - 2003 Oct 1
TI  - NMDA glutamate receptors are expressed by osteoclast precursors and involved in 
      the regulation of osteoclastogenesis.
PG  - 424-36
AB  - We previously identified functional N-methyl-D-aspartate (NMDA) glutamate 
      receptors in mature osteoclasts and demonstrated that they are involved in bone 
      resorption in vitro. In the present work, we studied the expression of NMDA 
      receptors (NMDAR) by osteoclast precursors and their role in osteoclastogenesis 
      using two in vitro models, the murine myelomonocytic RAW 264.7 cell line and 
      mouse bone marrow cells, both of which differentiate into osteoclasts in the 
      presence of macrophage colony-stimulating factor (M-CSF) and Rank ligand (RankL). 
      Using RT-PCR analysis with specific probes, we showed that RAW 264.7 cells and 
      mouse bone marrow cells express mRNA of NMDAR subunits NMDA receptor 1 (NR1) and 
      NMDA receptor 2 (NR2) A, B, and D. These subunits are expressed all along the 
      differentiation sequence from undifferentiated precursors to mature resorbing 
      osteoclasts. Semi-quantitative PCR analysis showed no regulation of the 
      expression of these subunits during the differentiation process. Two specific non 
      competitive antagonists of NMDAR, MK801 and DEP, dose-dependently inhibited 
      osteoclast formation in both models, indicating that osteoclastogenesis requires 
      the activation of NMDAR expressed by osteoclast precursors. MK801 had no effect 
      when added only during the first 2 days of culture, suggesting that NMDAR are 
      rather involved in the late stages of osteoclast formation. Finally, we 
      demonstrated using Western-blotting and immunofluorescence that activation of 
      NMDAR in RAW 264.7 cells by specific agonists induces nuclear translocation of 
      NF-kappa B, a factor required for osteoclast formation. Altogether, our results 
      indicate that osteoclast precursors express NMDAR that are involved in the 
      osteoclast differentiation process through activation of the NF-kappa B pathway.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Merle, Blandine
AU  - Merle B
AD  - INSERM Unit 403, Hopital E. Herriot, Pavillon F, 69437 LYON Cedex 03, France. 
      merle@lyon.inserm.fr
FAU - Itzstein, Cecile
AU  - Itzstein C
FAU - Delmas, Pierre D
AU  - Delmas PD
FAU - Chenu, Chantal
AU  - Chenu C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Carrier Proteins)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Subunits)
RN  - 0 (Pyrrolidines)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 34965-01-0 (1-(2-(dodecyloxy)ethyl)pyrrolidine hydrochloride)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/drug effects/metabolism
MH  - Brain/cytology/drug effects/metabolism
MH  - Carrier Proteins/metabolism
MH  - Cell Differentiation
MH  - Cell Nucleus/metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - *Gene Expression Regulation
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Monocytes/cytology/drug effects/metabolism
MH  - Myeloid Cells/cytology/drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Osteoclasts/*cytology/*drug effects/*metabolism
MH  - Protein Subunits
MH  - Protein Transport
MH  - Pyrrolidines/pharmacology
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/09/25 05:00
MHDA- 2004/05/28 05:00
CRDT- 2003/09/25 05:00
PHST- 2003/09/25 05:00 [pubmed]
PHST- 2004/05/28 05:00 [medline]
PHST- 2003/09/25 05:00 [entrez]
AID - 10.1002/jcb.10625 [doi]
PST - ppublish
SO  - J Cell Biochem. 2003 Oct 1;90(2):424-36. doi: 10.1002/jcb.10625.