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NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis.
J Cell Biochem. 2003 Oct 01; 90(2):424-36.JC

Abstract

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.

Authors+Show Affiliations

INSERM Unit 403, Hôpital E. Herriot, Pavillon F, 69437 LYON Cedex 03, France. merle@lyon.inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14505357

Citation

Merle, Blandine, et al. "NMDA Glutamate Receptors Are Expressed By Osteoclast Precursors and Involved in the Regulation of Osteoclastogenesis." Journal of Cellular Biochemistry, vol. 90, no. 2, 2003, pp. 424-36.
Merle B, Itzstein C, Delmas PD, et al. NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis. J Cell Biochem. 2003;90(2):424-36.
Merle, B., Itzstein, C., Delmas, P. D., & Chenu, C. (2003). NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis. Journal of Cellular Biochemistry, 90(2), 424-36.
Merle B, et al. NMDA Glutamate Receptors Are Expressed By Osteoclast Precursors and Involved in the Regulation of Osteoclastogenesis. J Cell Biochem. 2003 Oct 1;90(2):424-36. PubMed PMID: 14505357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis. AU - Merle,Blandine, AU - Itzstein,Cecile, AU - Delmas,Pierre D, AU - Chenu,Chantal, PY - 2003/9/25/pubmed PY - 2004/5/28/medline PY - 2003/9/25/entrez SP - 424 EP - 36 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 90 IS - 2 N2 - 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. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/14505357/NMDA_glutamate_receptors_are_expressed_by_osteoclast_precursors_and_involved_in_the_regulation_of_osteoclastogenesis_ L2 - https://doi.org/10.1002/jcb.10625 DB - PRIME DP - Unbound Medicine ER -