An active role for soluble and membrane intercellular adhesion molecule-1 in osteoclast activity in vitro

In osteoclastogenesis, the intercellular adhesion molecule (ICAM)-1 provides a high-affinity adhesion between the osteoblast and the osteoclast precursor, thereby facilitating the interaction between receptor activator nuclear factor kappaB ligand (RANKL) and its receptor RANK. However, the role of soluble ICAM (sICAM) in that process remains obscure. Therefore, the purpose of this study was to determine whether sICAM and ICAM-1 play an active role in the formation and maturation of osteoclasts. Monocytes isolated from healthy donors and cultured alone or with human osteoblast were stimulated with macrophage colony-stimulating factor, sRANKL, ICAM-1 monoclonal antibody (mAb), leucocyte function antigen (LFA)-1 mAb, and/or sICAM to produce mature osteoclasts. Release of TRAP 5b and resorption area were analyzed as markers of osteoclast formation and function, respectively. The effect of ICAM-1 and sICAM stimulation on apoptosis, cathepsin K, alphavbeta3, collagen-1, and on RANKL/osteoprotegerin (OPG)/RANK expression was evaluated. sICAM did not modify the release of TRAP 5b from osteoclast precursors in both mono and co-culture, but induced a significant increase in resorption area in both culture systems, as well as a positive effect on cathepsin K and alphavbeta3 protein expression. Cross-linking ICAM-1 on osteoblast resulted in increased RANKL mRNA and caspase-3 protein expression, decreased collagen-1 mRNA expression, and decreased osteoblast survival. Stimulation of preosteoclast with sICAM produced a significant increase in preosteoclast survival and a decrease in caspase-3 expression. These results indicate that ICAM-1 and sICAM have a dual effect on bone homeostasis, increasing osteoclast activity while lowering osteoblast anabolic activity.