EXPRESSION OF THE CELL-ADHESION MOLECULE VCAM-1 BY STROMAL CELLS IS NECESSARY FOR OSTEOCLASTOGENESIS

Osteoblastic cells have been shown to be involved in osteoclast format ion through cell to cell contacts. This study was designed to examine the possible function of vascular cell adhesion molecule 1 (VCAM-1) du ring osteoclastogenesis, As a source for stromal cells we used the rec ently established mouse bone marrow stromal cell line mBMS-B1 which ha s the ability to support osteoclastogenesis when used in co-culture wi th a crude spleen cell suspension, mBMS-B1 cells express a single simi lar to 3.9 kb VCAM-1 mRNA species, Expression was low under basal cult ure conditions and a 5-10-fold increase was observed in the presence o f 1,25(OH)(2)D-3. Cell surface expression of VCAM-1 examined by FACS a nalysis was increased about 2-fold after 1,25(OH)(2)D-3 treatment, Imm unoprecipitation of cell surface expressed VCAM-1 or total VCAM-1 prot ein using the anti-VCAM-1 monoclonal antibody MK2.7 resulted in a sing le similar to 110 kDa protein on SDS-PAGE, Induction by 1,25(OH)(2)D-3 was about 2-5-fold on day 3, The stromal cell-osteoclast precursor ce ll interaction was investigated in a co-culture of the mBMS-B1 and mou se spleen cells in the presence of 1,25(OH)(2)D-3, The monoclonal anti body MK2.7 which is known to block hemopoietic-stromal cell recognitio n inhibited the formation of osteoclasts when added to the co-culture at day 2 but not day 4, These data suggest that VCAM-1 is involved in the interaction between stromal cells and osteoclastic precursor cells during osteoclastogenesis presumably most important during early stag es of the formation of osteoclasts.