Emerging roles of osteocytes in skeletal homeostasis and mineral metabolism

Yifei Li, Jingyao Xu, Di Liu, Yudan Tian
2016 Int J Clin Exp Med   unpublished
Osteocytes constitute 90-95% of total bone cells and are derived from mesenchymal stem cell lineage through osteoblast differentiation. Osteocytes are dispersed throughout the bone matrix and display a dendritic morphology. The cell body of the osteocyte resides within a lacuna whereas the dendritic processes travel through the bone (called canalicular system) to reach the bone marrow. Osteocytes form a network of cells that is thought to mediate the effects of mechanical loading on bone
more » ... this extensive lacunocanalicular network via the participation of gap junctions/transmembrane channels that connect the cytoplasm of two adjacent osteocytes. The impact of mechanical strains on osteocytes is translated to the generation of signals from osteocytes that are considered critical in the regulation of bone resorption and bone formation, the two key fundamental processes that maintain skeletal homeostasis by bone modeling and remodeling. Activation of wingless tail (Wnt)/β-catenin canonical pathway in osteocytes induces osteogenic effect. On the other hand, osteocytes produce a SOST protein, sclerostin that antagonizes LDL-receptor-related protein-5/6 (LRP5/6)-mediated Wnt signaling and mediates an anti-osteogenic effect. Discovery of sclerostin has led to a neutralization approach wherein humanized monoclonal antibody against sclerostin has been developed to induce osteogenic effect and positioned as a therapy in post-menopausal osteoporosis. Osteocytes also produce fibroblast growth factor-23 (FGF-23) that regulates mineraliza-tion of bone extracellular matrix and mineral metabolism via the regulation of phosphate and vitamin D metabolism. Inactivating mutations of several osteocyte-specific genes cause hereditary hypophosphatemic disorders and min-eralization defects. This review aims to provide recent advances on the functionsof osteocytesin the regulation of bone remodeling and endocrine regulation of phosphate metabolism.