Osteocytes: central conductors of bone biology in normal and pathological conditions.

Osteocytes are the most abundant and longest-living cells in the adult skeleton. For a long time, osteocytes were considered static and inactive cells, but in recent years, it has been suggested that they represent the key responder to various stimuli that regulate bone formation and remodelling as well as one of the key endocrine regulators of bone metabolism. Osteocytes respond to mechanical stimuli by producing and secreting several signalling molecules, such as nitric oxide and prostaglandin E(2) , that initiate local bone remodelling. Moreover, they can control bone formation by modulating the WNT signalling pathway, an essential regulator of cell fate and commitment, as they represent the main source of sclerostin, a negative regulator of bone formation. Osteocytes can also act as an endocrine organ by releasing fibroblast growth factor 23 and several other proteins (DMP-1, MEPE, PHEX) that regulate phosphate metabolism. It has been demonstrated that various bone diseases are associated with osteocyte abnormalities, although it is not clear if these changes are the direct cause of the pathology or if they are secondary to the pathological changes in the bone microenvironment. Thus, a better understanding of these cells could offer exciting opportunities for new advances in the prevention and management of different bone diseases.