Development and application of the control methods against alveolar bone resorption using human monoclonal antibody

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Osteoclasts, bone resorbing multinucleated cells, develop from monocyte-macrophage lineage cells in the presence of receptor activator NF-kB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). M-CSF-dependent bone marrow macrophages from mouse bone marrow cells have been shown to differentiate into osteoclast-like multinucleated cells (OCLs) in the presence of soluble RANKL and M-CSF. To investigate human biological responses, it is better to use human-derived proteins, such as human recombinant proteins and monoclonal antibodies. In the present study, we established human hybridomas secreting antibodies against RANKL using in vivo immunization of peripheral blood lymphocytes, and obtained some positive clones. We found that human anti-RANKL monoclonal antibody partially suppress the formation of OCL in vitro. Next, we tried to establish a method of in vivo electroporation to control the inflammatory bone resorption using human anti-RANKL antibody. However, we have no positive results in this study. Further work is needed to put a human monoclonal antibody against RANKL to practical use. Taken together, these results suggest that human monoclonal antibody against RANKL may be useful to control the inflammatory bone resorption in periodontitis.