INVOLVEMENT OF ADHESION MOLECULES LFA-1 AND ICAM-1 IN OSTEOCLAST DEVELOPMENT

We report here that leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) are involved in osteoclast development. Osteoclast development was observed on co-culture of mouse spleen cells and mouse bone marrow derived clonal stromal cells, TMS-14, in the presence of 1alpha,25-dihydroxyvitamin D-3 (1alpha,25-(OH)2D3) for 8 days, and quantified with respect to tartrate-resistant acid phosphatase (TRACP) activity. When either one of the monoclonal antibodies (MAbs) to mouse LFA-1 and mouse ICAM-1 was added to the co-culture system, the TRACP activity was significantly inhibited. The experiment in which one-day treatment with each of these MAbs was performed during the 8 days of cultivation showed that the inhibitory effects of both MAbs on the TRACP activity at 8 days were observed from an early stage of the culture, but were more notable at a later stage (days 4-6). As the expression of ICAM-1 was observed on both spleen cells and TMS-14, we next examined whether the interaction between stromal cells and osteoclast progenitors or among osteoclast progenitors was more important for osteoclast development. To determine this, rat spleen cells and a MAb to rat ICAM-1 were used instead of those of mouse. When MAb to rat ICAM-1 or mouse ICAM-1 was added to the co-culture system of rat spleen cells and TMS-14, the inhibitory effect of the MAb to rat ICAM-1 was mainly observed at a later stage of the culture period and that of anti-mouse ICAM-1 antibody was only observed at an earlier stage. These results indicate that adhesion molecules LFA-1 and ICAM-1 may play a role in osteoclast development via interaction between stromal cells and osteoclast progenitors as well as among osteoclast progenitors.