The osteocyte: key player in regulating bone turnover

Abstract

Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell-cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading.

Keywords: Bone Mineral Density; Cytokines; Osteoarthritis; Osteoporosis.

Figure 1

Osteocyte-derived receptor activator of NF-κB ligand (RANKL) increases bone resorption. Osteocytes control unloading-induced bone loss by induction of RANKL in osteocytes, which results in increased osteoclast-mediated bone resorption.

Figure 2

Osteocyte-derived sclerostin and Dickkopf-related protein 1 (DKK-1) regulate bone formation. Loading decreases osteocyte-derived sclerostin and DKK-1, which results in activation of the Wnt/β-catenin signaling in osteoblasts and increased bone formation.