Gray C, Marie H, Arora M, Tanaka K, Boyde A, Jones S, Attwell D
Department of Anatomy, University College London, United Kingdom.
J Bone Miner Res. 2001 Apr;16(4):742-9. doi: 10.1359/jbmr.2001.16.4.742.
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.
骨细胞表达谷氨酸门控的钙离子通透型N-甲基-D-天冬氨酸（NMDA）受体和GLAST谷氨酸转运体。据报道，阻断NMDA受体会减少破骨细胞产生的骨吸收陷窝数量，而机械负荷会改变GLAST转运体的表达，这会改变细胞外谷氨酸浓度和NMDA受体的激活。因此，类比于大脑，谷氨酸被假定为骨中一种重要的细胞间信使，控制着骨的形成和吸收。我们发现，激活或阻断NMDA受体对培养的大鼠成骨细胞的骨形成没有影响。NMDA受体阻断剂MK-801可减少破骨细胞产生的吸收陷窝数量，但另一种阻断剂AP-5则没有此作用，这意味着MK-801的这种作用与其谷氨酸阻断作用无关。相比之下，MK-801、AP-5和NMDA对陷窝体积没有一致的影响。在敲除GLAST谷氨酸转运体的小鼠中，与野生型同窝小鼠相比，在下颌骨和长骨的大小、形态、小梁结构、肌肉附着区域、吸收腔隙或骨形成与吸收区域方面未检测到差异。这些数据表明，谷氨酸在控制骨生长中不发挥主要作用。
