Osteoclasts are responsible for bone resorption and can be derived from the mononuclear macrophage system in the bone marrow; hence, a method should be developed to differentiate macrophage colony-stimulating factor. Signal transduction in osteoclast formation and cell differentiation are mediated by osteoprotegerin(OPG) and nuclear factor kappa B(NF-κB), particularly its receptor-activating factor(RANK) and ligand(RANKL) system. The RANKL-RANK-OPG signal transduction pathway is affected by several factors, including the signal transduction pathway of NF-κB, mitogen-activated protein kinase, and phosphatidylinositol-3-kinase protein. Tumor necrosis factor-α can stimulate osteoblasts to produce granulocyte–macrophage colony-stimulating factor and interleukin(IL)-6 factor, thus inducing osteoclast precursors to differentiate into osteoclasts. Nitric oxide and estrogen may affect osteoclast differentiation precursors. The tyrosine kinase of integrin αvβ3 in osteoclast-induced tyrosine phosphorylation and proline-rich 2 region and the non-receptor-dependent protein tyrosine kinase of the Src family of adaptor proteins and P130 Crk-related proteins are important in the activation of substrates, and thus, in bone absorption. In osteoclasts and their precursors, the receptor family of transforming growth factor-β, steroid receptors, G-protein coupled receptors, IL-1, and non-tyrosine kinase cell factor are important for osteoclast function.
