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Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate.
Eur J Pharmacol. 2008 Jul 28; 589(1-3):37-44.EJ

Abstract

Glutamate, an important central excitatory neurotransmitter, is also secreted by osteoblasts and may be involved in the regulation of bone metabolism. Glutamate receptors for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) are demonstrated in bone cells. Here we investigated the in vivo effects of glutamate by local injection of AMPA, NMDA, and their antagonists into tibia as well as their in vitro effects on the maturation of osteoblasts and formation of osteoclasts. AMPA receptor antagonist CNQX and NMDA receptor antagonist MK-801 significantly inhibited the maturation and mineralization of osteoblasts in high-glutamate alpha-MEM. On the other hand, AMPA and NMDA up-regulated the mineralized deposition and osteocalcin mRNA expression of primary osteoblasts cultured in glutamate-free DMEM. AMPA and NMDA induced the phosphorylation of extracellular signal-related kinases (ERK) in osteoblasts within 15 min. In addition, NMDA but not AMPA up-regulated the number of osteoclasts while MK801 antagonized this potentiating effect. To explore the action of glutamate agonists on bone formation in animal model, AMPA was locally injected into tibia and it was found that the bone volume in secondary spongiosa significantly increased and co-treatment of CNQX antagonized the enhancing effect of AMPA. These results suggest that glutamate may play a physiological role in regulating the maturation of osteoblasts and osteoclastogenesis. Activation of both AMPA and NMDA receptors regulates the maturation of osteoblasts. NMDA but not AMPA affects receptor for activation of NF-kappaB ligand (RANKL)-induced osteoclastogenesis.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, National Taiwan University and Hospital, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18538763

Citation

Lin, Tzu-Hung, et al. "Regulation of the Maturation of Osteoblasts and Osteoclastogenesis By Glutamate." European Journal of Pharmacology, vol. 589, no. 1-3, 2008, pp. 37-44.
Lin TH, Yang RS, Tang CH, et al. Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate. Eur J Pharmacol. 2008;589(1-3):37-44.
Lin, T. H., Yang, R. S., Tang, C. H., Wu, M. Y., & Fu, W. M. (2008). Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate. European Journal of Pharmacology, 589(1-3), 37-44. https://doi.org/10.1016/j.ejphar.2008.04.060
Lin TH, et al. Regulation of the Maturation of Osteoblasts and Osteoclastogenesis By Glutamate. Eur J Pharmacol. 2008 Jul 28;589(1-3):37-44. PubMed PMID: 18538763.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate. AU - Lin,Tzu-Hung, AU - Yang,Rong-Sen, AU - Tang,Chih-Hsin, AU - Wu,Ming-Yueh, AU - Fu,Wen-Mei, Y1 - 2008/05/08/ PY - 2007/11/05/received PY - 2008/04/10/revised PY - 2008/04/23/accepted PY - 2008/6/10/pubmed PY - 2008/10/25/medline PY - 2008/6/10/entrez SP - 37 EP - 44 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 589 IS - 1-3 N2 - Glutamate, an important central excitatory neurotransmitter, is also secreted by osteoblasts and may be involved in the regulation of bone metabolism. Glutamate receptors for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) are demonstrated in bone cells. Here we investigated the in vivo effects of glutamate by local injection of AMPA, NMDA, and their antagonists into tibia as well as their in vitro effects on the maturation of osteoblasts and formation of osteoclasts. AMPA receptor antagonist CNQX and NMDA receptor antagonist MK-801 significantly inhibited the maturation and mineralization of osteoblasts in high-glutamate alpha-MEM. On the other hand, AMPA and NMDA up-regulated the mineralized deposition and osteocalcin mRNA expression of primary osteoblasts cultured in glutamate-free DMEM. AMPA and NMDA induced the phosphorylation of extracellular signal-related kinases (ERK) in osteoblasts within 15 min. In addition, NMDA but not AMPA up-regulated the number of osteoclasts while MK801 antagonized this potentiating effect. To explore the action of glutamate agonists on bone formation in animal model, AMPA was locally injected into tibia and it was found that the bone volume in secondary spongiosa significantly increased and co-treatment of CNQX antagonized the enhancing effect of AMPA. These results suggest that glutamate may play a physiological role in regulating the maturation of osteoblasts and osteoclastogenesis. Activation of both AMPA and NMDA receptors regulates the maturation of osteoblasts. NMDA but not AMPA affects receptor for activation of NF-kappaB ligand (RANKL)-induced osteoclastogenesis. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18538763/Regulation_of_the_maturation_of_osteoblasts_and_osteoclastogenesis_by_glutamate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00481-0 DB - PRIME DP - Unbound Medicine ER -