The role of glutamate transporters in bone cell signalling

The amino acid L-glutamate mediates signals at excitatory synapses in the CNS where its effects are controlled by co-ordinated activities of various types of glutamate receptor and transporter. This signalling mechanism has proved to be far more ubiquitous with many different cell types responding to glutamate. The glutamate transporter GLAST-1 was the first component of this pathway identified in bone where its expression was found to be mechanoresponsive in osteocytes. There is now a wealth of evidence supporting a role for this signalling mechanism in bone. Osteoblasts can release glutamate in a regulated manner and express functional glutamate receptors that influence their differentiation and osteogenic activity. Likewise, osteoclasts express functional glutamate receptors that influence their bone resorbing capacity. This article considers the various functions of glutamate transporters in this signalling pathway, and the evidence supporting an important role of glutamate signalling in regulating bone cell activities.