dizocilpine-maleate and Bone-Diseases--Metabolic

Bone cells express glutamate-gated Ca2+-permeable N-methyl-D-aspartate (NMDA) receptors and GLAST glutamate transporters. Blocking NMDA receptors has been reported to reduce the number of bone resorption pits produced by osteoclasts, and mechanical loading alters GLAST transporter expression, which should change the extracellular glutamate concentration and NMDA receptor activation. Thus, by analogy with the brain, glutamate is postulated to be an important intercellular messenger in bone, controlling bone formation and resorption. We found that activating or blocking NMDA receptors had no effect on bone formation by rat osteoblasts in culture. The number of resorption pits produced by osteoclasts was reduced by the NMDA receptor blocker MK-801 but not by another blocker AP-5, implying that this effect of MK-801 is unrelated to its glutamate-blocking action. By contrast, MK-801, AP-5, and NMDA had no consistent effect on the volume of pits. In mice with GLAST glutamate transporters knocked out, no differences were detected in mandible and long bone size, morphology, trabeculation, regions of muscle attachment, resorption lacunae, or areas of formation versus resorption of bone, compared with wild-type siblings. These data suggest that glutamate does not play a major role in controlling bone growth.

Topics: 2-Amino-5-phosphonovalerate; Alveolar Bone Loss; Amino Acid Transport System X-AG; Animals; Animals, Newborn; ATP-Binding Cassette Transporters; Biological Transport; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Cells, Cultured; Dizocilpine Maleate; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Femur; Glutamic Acid; Glycine; Humerus; Mandible; Mice; Mice, Knockout; Models, Animal; N-Methylaspartate; Osteoblasts; Osteoclasts; Osteogenesis; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate