Studies on the origin, identification, and characterization of osteoclasts have been difficult. This is in part due to a lack of definitive osteoclast markers and the similarity of these cells in form and function to cells of the mononuclear phagocyte system. To solve this problem, we inoculated isolated chick osteoclasts into mice to generate osteoclast-specific monoclonal antibodies. Supernatants from growth-positive hybridomas were screened by indirect immunofluorescent methods against cultured osteoclasts, monocyte-derived multinucleated giant cells, cultured monocytes, fibroblasts, and limb mesenchyme. Select hybridomas were cloned to produce 375 clones, which were analyzed as described above. Antibody from select clones was also reacted with paraffin sections of bone. In addition, two clones have been analyzed by enzyme-linked immunosorbent asssay (ELISA) and Western blot analysis. Antibody binding from an osteoclast-specific clone and a clone reactive with osteoclasts, giant cells, and cultured monocytes (as determined by immunohistochemical assay) was confirmed by antibody-binding and titration curves quantitated by ELISA. The above studies demonstrate that osteoclast specific antigens exist, and that osteoclasts, giant cells, and cultured monocytes share common determinants not found on other cells screened.The multinucleated osteoclast serves as the major cell type responsible for degradation of bone matrix, and its importance in bone growth, skeletal remodeling, and electrolyte homeostasis has been well established (1-3). The mechanisms and regulation of osteoclast-mediated bone resorption are not yet clearly understood; moreover, little is known about the recruitment and differentiation of osteoclast precursors (4, 5). It is generally believed that osteoclasts originate from cells belonging to the mononuclear phagocyte system (6-8). Although different, macrophages and osteoclasts share certain similarities in form and function, including membrane folding (9), positive acid phosphatase staining, activity of other lysosomal enzymes, and the ability to degrade connective tissue (2, 10). Chick-quail chimera studies (l l, 12) have demonstrated a blood-borne origin for the osteoclast, and parabiosis and marrow transplantation have been successfully used to correct the osteoclast defect in osteopetrosis (13,14). Together, these observations support the hypothesis that osteoclasts are polykaryons that derive from circulating mononuclear cells belonging to the monocyte-macrophage family.In various cell populations, a seemingly homogeneous phenotype can now be divided into functional subpopulations with monoclonal antibodies raised to unique cell surface components. In this regard, mononuclear phagocytes have been shown to play important roles as antigen-presenting cells (15), cytotoxic effector cells (16), and also as secretory cells 1592 (17). Recently, it has been demonstrated by the use of monoclonal antibody technology that one cell type may not be responsible for all functions. In this context, ...
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