The skeleton is a surprisingly dynamic tissue that remodels throughout life in humans.  I study factors that control the function of the three main bone cell types: osteoblasts (bone-forming connective tissue cells), osteocytes (network of ex-osteoblasts resident in bone matrix) and osteoclasts (specialised bone-destroying cells, derived from haematopoietic system).  I am particularly interested in two ‘fundamental’ regulators, hypoxia and acidosis, which are, respectively, major stimulators of the formation and resorptive (destructive) activities of osteoclasts.  At the same time, hypoxia and acidosis exert profound reciprocal actions on osteoblasts by respectively blocking their growth / differentiation (and thus bone formation) and ability to mineralise bone.  These responses provide insights into the pathogenesis of common bone loss disorders.  A separate line of research is focussed on the ability of extracellular ATP to block mineralisation in bone and vascular smooth muscle.  This effect appears to be partly mediated by P2 receptors for ATP but, perhaps more importantly, via the enzymic breakdown of ATP outside cells to produce pyrophosphate, the body’s ubiquitous ‘natural water softener’.