The role of glutamate in the regulation of bone mass and architecture

Communication between the cells in bone underlies the way that the tissue functions physiologically, and in nearly all pathologies, the pathogenesis of skeletal diseases. The number of molecules involved in intercellular signalling in bone grows constantly and it is perhaps unsurprising that the list includes many with functions in other tissues. In recent years, evidence has accumulated to show that molecules involved in neurotransmission have paracrine roles in the skeleton. The focus of this review is the excitatory amino acid glutamate and its role in regulating bone formation and resorption. Specifically, this article will concentrate on the functional role of the system, and the reasons why mechanisms like synaptic transmission are relevant to what might appear to be a slow responding tissue, as the sites of expression of glutamate signalling components in bone have been reviewed already. While there is strong evidence for a regulatory role for glutamate in osteoblast and osteoclast differentiation and function in vitro, in vivo data is less advanced. Preliminary data from in vivo systems does however suggest that glutamate has a physiological function in the skeleton.