'Pre-synaptic' vesicular glutamate release mechanisms in osteoblasts.
Identification of intercellular signalling pathways in bone represents an important therapeutic target for drug development in the treatment of clinical conditions such as osteoporosis. One such intercellular signalling pathway in bone appears to be mediated by the excitatory amino acid glutamate, exhibiting remarkable similarities to synaptic neurotransmission. Bone cells (osteoblasts and osteoclasts) express functional glutamate receptors that are electrophysiologically and pharmacologically similar to those expressed in the CNS and there is evidence for their involvement in both bone formation and bone resorption. However, to date the cellular source of glutamate for the activation of these specific glutamatergic receptors in bone has remained unclear. This review provides a synopsis of our current understanding of these 'pre-synaptic' signalling mechanisms, presenting compelling evidence that osteoblasts possess the molecular capability to direct regulated vesicular glutamate release in response to osteotropic regulatory inputs. In addition, we discuss mechanisms other than 'pre-synaptic' glutamatergic mechanisms that could account for the source of glutamate for receptor activation in osteoblasts. Finally, convincing evidence reporting physiologically released glutamate in varied osteoblasts and osteoblastic cell lines is discussed. The overwhelming conclusion of this review is that by defining both the characteristics and regulatory control of this process, highlighting both similarities and differences between the CNS and bone may provide compelling evidence for the role of glutamate in bone cell function and physiology.
Bhangu
P S
PS
Department of Biology, University of York, York, UK. bhanguj@iconuk.com