The osteocyte: the underestimated conductor of the bone orchestra

The osteocyte is often considered to be a cell that is hardly active, yet it turns out to have a central role in bone remodeling. It functions as a mechanoreceptor that translates mechanical stimuli into biochemical signals. The expression of PGE2 by loaded osteocytes and the consequent activation of the cAMP/PKA pathway, together with stabilization of beta-catenin, may permit cross talk with the canonical Wnt/beta-catenin pathway, the activation of which is increased by the load-dependent reduction of the expression of DKK1 and of sclerostin (Sost, the secretion product of old osteocytes). These signal pathways, as well as TGF-beta and BMP expression, stimulate the differentiation and activity of osteoblasts, reduce their apoptosis, and enhance bone formation. The expressions of MEPE, FGF-23 and DMP-1 further contribute to the osteocytic control of bone metabolism. Periosteocytic osteolysis, if definitively demonstrated, would constitute another fundamental function of osteocytes. A thorough understanding of the osteocyte's activities could open up new strategies in the therapy of metabolic bone diseases.