Functional osteoblastic ionotropic glutamate receptors are a prerequisite for bone formation

Many studies have now demonstrated that osteoblasts express the protein components necessary for functional neuronal-like glutamatergic signalling to occur, and as a result a physiological role for receptor mediated osteoblastic glutamate signalling has been proposed. Osteoblastic ionotropic type glutamate receptors (iGluRs) have been shown to be functional; they possess electrophysiological characteristics similar to neuronal iGluR) and agonist application modulates the activity of intracellular signalling molecules and osteoblastic transcription factors. The physiological importance of osteoblastic iGluRs is illustrated by the fact that osteoblasts treated in vitro with non-competitive iGluR antagonists fail to form mineralized bone. Interestingly compounds known to antagonize specific sub-types of iGluR induce different effects when applied to osteoblasts derived from long and flat bones. These data imply that not only are functional osteoblastic iGluRs a prerequisite for osteoblast differentiation and bone formation, but also that the components of osteoblastic glutamatergic signalling may be adapted to reflect the differential function of osteoblasts from different skeletal sites. This paper reviews the evidence that suggests that iGluR-mediated glutamate signalling plays a fundamental role in the regulation of osteoblast function and bone formation, and discusses the therapeutic potential of manipulation of osteoblastic iGluR to modulate bone homeostasis.