Specific antagonists of NMDA receptors prevent osteoclast sealing zone formation required for bone resorption

Cecile Itzstein, L Espinosa, P D Delmas, C Chenu

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

N-Methyl-d-aspartate (NMDA) glutamate receptors, widely distributed in the nervous system, have recently been identified in bone. They are expressed and are functional in osteoclasts. In the present work, we have studied the effects of specific antagonists of NMDA receptors on osteoclast activation and bone resorption. Using an in vitro assay of bone resorption, we showed that several antagonists of NMDA receptors binding to different sites of the receptor inhibit bone resorption. Osteoclast activation requires adhesion to the bone surface, cytoskeletal reorganization and survival. We demonstrated by autoradiography that the specific NMDA receptor channel blocker, MK 801, binds to osteoclasts. This antagonist had no effect on osteoclast attachment to bone and did not induce osteoclast apoptosis. In contrast, MK 801 rapidly decreased the percentage of osteoclasts with actin ring structures that are associated with actively resorbing osteoclasts. These results suggest that NMDA receptors expressed by osteoclasts may be involved in adhesion-induced formation of the sealing zone required for bone resorption.
Original languageEnglish
Pages (from-to)201-9
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume268
Issue number1
DOIs
Publication statusPublished - 5 Feb 2000

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Osteoclasts
Bone Resorption
Bone
Dizocilpine Maleate
Bone and Bones
Adhesion
Chemical activation
aspartic acid receptor
Glutamate Receptors
Neurology
Autoradiography
Aspartic Acid
Nervous System
Actins
Assays
Apoptosis

Keywords

  • Actins
  • Animals
  • Apoptosis
  • Autoradiography
  • Bone Resorption
  • Cattle
  • Cell Adhesion
  • Cell Survival
  • Dizocilpine Maleate
  • Excitatory Amino Acid Antagonists
  • Osteoclasts
  • Receptors, N-Methyl-D-Aspartate

Cite this

Specific antagonists of NMDA receptors prevent osteoclast sealing zone formation required for bone resorption. / Itzstein, Cecile; Espinosa, L; Delmas, P D; Chenu, C.

In: Biochemical and Biophysical Research Communications, Vol. 268, No. 1, 05.02.2000, p. 201-9.

Research output: Contribution to journalArticle

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N2 - N-Methyl-d-aspartate (NMDA) glutamate receptors, widely distributed in the nervous system, have recently been identified in bone. They are expressed and are functional in osteoclasts. In the present work, we have studied the effects of specific antagonists of NMDA receptors on osteoclast activation and bone resorption. Using an in vitro assay of bone resorption, we showed that several antagonists of NMDA receptors binding to different sites of the receptor inhibit bone resorption. Osteoclast activation requires adhesion to the bone surface, cytoskeletal reorganization and survival. We demonstrated by autoradiography that the specific NMDA receptor channel blocker, MK 801, binds to osteoclasts. This antagonist had no effect on osteoclast attachment to bone and did not induce osteoclast apoptosis. In contrast, MK 801 rapidly decreased the percentage of osteoclasts with actin ring structures that are associated with actively resorbing osteoclasts. These results suggest that NMDA receptors expressed by osteoclasts may be involved in adhesion-induced formation of the sealing zone required for bone resorption.

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