Glutamate does not play a major role in controlling bone growth

Bone cells express glutamate-gated Ca2+-permeabIe N-methyl-D-aspartate (NMD A) receptors and GLAST glutamate transporters. Blocking NMDA receptors has been reported to reduce the number of bone resorption pits produced by oste oclasts, and mechanical loading alters GLAST transporter expression, which should change the extracellular glutamate concentration and NMDA receptor a ctivation. Thus, by analogy with the brain, glutamate is postulated to be a n important intercellular messenger in bone, controlling bone formation and resorption, We found that activating or blocking NMDA receptors had no eff ect on bone formation by rat osteoblasts in culture, The number of resorpti on 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 i s unrelated to its glutamate-blocking action. By contrast, MK-801, AP-5, an d NMDA had no consistent effect an the volume of pits. In mice with GLAST g lutamate transporters knocked out, no differences were detected in mandible and long bone size, morphology, trabeculation, regions of muscle attachmen t, resorption lacunae, or areas of formation versus resorption of bone, com pared with wild-type siblings. These data suggest that glutamate does not p lay a major role in controlling bone growth.