Expression of an N-methyl-D-aspartate-type receptor by human and rat osteoblasts and osteoclasts suggests a novel glutamate signaling pathway in bone

Bone. 1998 Jun;22(6):645-9. doi: 10.1016/s8756-3282(98)00061-1.


Signaling between the various types of cells found in bone is responsible for controlling the activity of osteoblasts and osteoclasts, and therefore the regulation of bone mass. Our identification of a neuronal glutamate transporter in osteoblasts and osteocytes suggests the possibility that bone cells may use the excitatory amino acid glutamate as a signaling molecule. In these studies we report the expression of different subtypes of glutamate receptors in osteoblasts and osteoclasts in vitro and in vivo. We have identified expression in human and rat bone cells of N-methyl-D-aspartate receptor-1 (NMDAR-1) and 2D subunits and PSD-95, the NMDA receptor clustering protein associated with signaling in the central nervous system. In situ hybridization and immunohistochemistry localized NMDAR-1 expression to osteoblasts and osteoclasts in human tissue sections. These findings strengthen the suggestion that glutamate is involved in signaling between bone cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Amino Acid Transport System X-AG
  • Animals
  • Base Composition
  • Biological Transport
  • Disks Large Homolog 4 Protein
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Guanylate Kinases
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mice
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, N-Methyl-D-Aspartate / biosynthesis*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Signal Transduction / genetics


  • ATP-Binding Cassette Transporters
  • Amino Acid Transport System X-AG
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NMDA receptor A1
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • postsynaptic density proteins
  • Glutamic Acid
  • Guanylate Kinases