INVOLVEMENT OF LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 AND INTERCELLULAR-ADHESION MOLECULE-1 IN OSTEOCLASTOGENESIS - A POSSIBLE ROLE IN DIRECT INTERACTION BETWEEN OSTEOCLAST PRECURSORS

In our search for molecules involved in the process of osteoclast diff erentiation, we examined the surface phenotypes of the preosteoclast-l ike cells and osteoclast-like multinucleated cells (MNCs) formed in bo ne marrow cultures, using monoclonal antibodies recognizing different antigen molecules expressed on hematopoietic cells. Among these cell s urface antigens, lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) were highly expressed on mo nonuclear cells in the cultures for forming preosteoclast-like mononuc lear cells. The double detection of these two antigen molecules with o steoclast-specific antigen and with calcitonin receptor, using a fluor escence-activated cell sorter or autoradiography technique, revealed t hat LFA-1 and ICAM-1 were expressed on the preosteoclasts. The express ion of ICAM-1 was detected on both preosteoclasts and osteoclast-like MNCs, whereas the expression of LFA-1 was restricted to preosteoclasts . We designed a peptide with the sequence of the binding site of ICAM- 1 against the ligand LFA-1. In the whole bone marrow culture system fo r forming osteoclast-like MNCs, a significant inhibition of MNC format ion was observed by the addition of this peptide. These results strong ly suggest the involvement of an LFA-1/ICAM-1-interaction in osteoclas togenesis.