Osteoclast development: the cell surface and the bone environment

Bone development and remodelling processes depend on complex interactions between bone cell precursors, mature bone cells, extracellular matrix molecules, growth factors, the immune system and humoral factors. The exact molecular nature of many of the cell-cell and cell-matrix interactions occurring during bone remodelling remains to be resolved. Cell surface molecules are likely to have important roles in both bone cell differentiation and regulatory processes. However, little is known about changes in the osteoclast cell surface during development and there is only limited information on the cell surface composition of the mature cell phenotype. We describe how one osteoclast-specific monoclonal antibody has been used to identify, characterize and purify a 96 kDa/140 kDa osteoclast membrane protein. The antibody has also been used as a phenotypic marker in studies designed to identify soluble and matrix-related bone factors involved in the terminal stages of osteoclast differentiation. In parallel studies using marrow-derived giant cells and the chick chorioallantoic membrane (CAM), immunohistochemical and enzyme-linked immunoassays (ELISA) have been used to investigate the influence of calvaria, calvaria-conditioned medium, bone matrix, and bone matrix components on osteoclast development. Marrow-derived giant cells express osteoclast-specific cell surface antigens when co-cultured with live calvariae or when exposed to calvaria-conditioned medium. In the richly vascularized and mesenchymal cell-containing CAM, intact bone matrix induces the formation of giant cells that express the osteoclast-specific antigens. In contrast, isolated bone matrix components implanted on the CAM recruit only mononuclear cells which are not recognized by the osteoclast-specific antibody.