Our work falls into 3 main areas:

1. ACIDOSIS. We discovered that a small pH reduction (acidosis) is necessary to activate osteoclasts to excavate resorption pits on bone surfaces. Simultaneously, acidosis prevents mineralisation of newly-formed bone by osteoblasts. The responses of bone cells to extracellular pH changes probably represent a primitive 'failsafe' to correct systemic acidosis by releasing alkaline bone mineral. Acidosis due to disease (eg, cancer, diabetes, kidney failure) or ageing could play a role in bone loss disorders. Current research is focused on understanding the mechanisms by which bone cells recognise and respond to pH changes in their environment.

2. HYPOXIA. We found that hypoxia (low oxygen) is a major stimulator of the formation of osteoclasts from mononuclear precursor cells present in blood and bone marrow. Osteoclast formation - and thus bone destruction - is strongly increased when oxygen is reduced to as little as 1% of the atmospheric level. In contrast, we observed that hypoxia blocks the growth and bone-forming capacity of osteoblasts. These observations may help to explain why bone is rapidly lost when the blood supply is reduced or disrupted , eg, as a result of inflammation, tumours, fractures, diabetes, airway diseases and ageing. Significantly, hypoxia also causes tissue acidosis (see above). Our results emphasise the critical role of the vasculature in the maintenance of bone health.

3. NUCLEOTIDES. ATP and other nucleotides, acting through P2 receptors, play important and complex regulatory roles as messenger molecules for cell-to-cell communication. We found that numerous P2 receptors are expressed by bone cells and that low concentrations of ATP stimulate both the formation and activity of osteoclasts, whilst selectively blocking mineralisation of newly formed bone by osteoblasts. Recent results show that skeletal changes can occur when P2 receptors are defective or deficient. This works suggests that the ATP , P2 cell signalling system offers potential for novel bone therapeutics.