Cytokines and Bone

Bone turnover is due to cyclic bone resorption followed by bone apposition; these processes are due to the coordinated actions of osteoclasts (OCs) and osteoblasts (OBs). The actions of these two cellular types are orchestrated by osteocytes (OS) that differentiate from osteoblasts and are the most abundant cells in bone. OCs are formed by the attraction of myelomonocytic precursors to the resorption site; the fusion of these cells generates a multinucleated cell attached to the bone surface. OBs derive from a mesenchymal stem cell precursor shared with adipocytes. OS are thought to be the cells primarily responsible for mechanosensing in bone. Numerous cytokines are thought to be responsible for the regulation of bone turnover; most of them have pleiotropic actions and are involved in the regulation of systems other than skeleton. OC formation and function are mainly regulated by the essential factor RANKL, whereas other cytokines increased during inflammation up-regulate OCs and are involved in inflammation-induced bone loss. OB formation and activity are believed to be mainly regulated by the Wnt and BMP signalling pathways. This review will focus on the main cytokines involved in the regulation of osteoclastogenesis, osteoblastogenesis and coupling of osteoclasts and osteoblasts under physiological and pathological conditions.