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NMDA Receptor in Bone

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The NMDA Receptors

Part of the book series: The Receptors ((REC,volume 30))

Abstract

A view that l-glutamic acid (Glu) plays a role as an excitatory amino acid neurotransmitter through mechanisms relevant to activities of a variety of signaling machineries essential for the neurocrine at synapses in the brain is prevailing. Although expression of functional receptors is an absolute requirement for the glutamatergic signal input in the brain, recent molecular biological and pharmacological studies including ours give rise to a novel concept for Glu as an extracellular signal mediator in the autocrine and/or paracrine system in several non-neuronal tissues outside the brain. We have demonstrated functional expression of a variety of glutamatergic signaling machineries by bone-forming osteoblasts and mechano-sensing osteocytes in bone, in addition to chondrocytes in cartilage, which are all derived from primitive mesenchymal stem cells in bone marrows. We could also detect functional expression of the cystine/Glu antiporter comprised of both xCT and 4F2hc subunits, rather than any other glutamatergic signaling machineries, by bone-resorbing osteoclasts believed to originate in hematopoietic stem cells. On the basis of these findings, we would propose a universal role of Glu as an extracellular signal mediator in the neurocrine, autocrine and paracrine systems in our body. Clinical aspect is also discussed on dietary Glu intake with a focus on possible benefits for the prophylaxis and/or treatment of osteoporosis.

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Abbreviations

AMPA:

dl-α-amino-3-hydroxy-5-methylisoxasole-4-propionate

EAAC1:

Excitatory amino acid carrier 1

EAAT:

Excitatory amino acid transporter

GLAST:

Glutamate aspartate transporter

GLT-1:

Glutamate transporter-1

Glu:

Glutamate

GluR:

Glutamate receptor

GSH:

Reduced glutathione

iGluR:

Ionotropic glutamate receptor

KA:

Kainate

M-CSF:

Macrophage-colony stimulating factor

mGluR:

Metabotropic glutamate receptor

MK-801:

Dizocilpine

MNCs:

Multinucleated cells

MSCs:

Mesenchymal stem cells

NMDA:

N-methyl-d-aspartate

NMDAR:

N-methyl-d-aspartate receptor

RA:

Rheumatoid arthritis

RANK:

Receptor activator of NF-κB

RANKL:

Receptor activator of NF-κB ligand

Runx2:

Runt-related transcription factor-2

TRAP:

Tartrate resistant acid phosphatase

VGLUT:

Vesicular glutamate transporter

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Acknowledgement

The author is highly indebted to all colleagues listed in the references cited in this chapter for their excellent and enthusiastic efforts to support experimental studies for a period from 1999 to 2015 in Laboratory of Molecular Pharmacology, Kanazawa University Graduate School.

Conflict of interest:

The author has no conflict of interest.

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Authors and Affiliations

  1. Section of Prophylactic Pharmacology, Kanazawa University Venture Business Laboratory, Room 402, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan

    Yukio Yoneda Ph.D.

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  1. Yukio Yoneda Ph.D.
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Correspondence to Yukio Yoneda Ph.D. .

Editor information

Editors and Affiliations

  1. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan

    Kenji Hashimoto

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Yoneda, Y. (2017). NMDA Receptor in Bone. In: Hashimoto, K. (eds) The NMDA Receptors. The Receptors, vol 30. Humana Press, Cham. https://doi.org/10.1007/978-3-319-49795-2_8

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