EFFECTS OF RECOMBINANT HUMAN OSTEOGENIC PROTEIN-1 ON THE DIFFERENTIATION OF OSTEOCLAST-LIKE CELLS AND BONE-RESORPTION

Recombinant human OP-1 stimulated the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) significantly and in a dose-dependent manner in rat bone marrow cell culture. Newly formed MNCs either induced by hOP-1 alone or with 1,25(OH)(2)D-3 were also positive for vitronectin receptor and carbonic anhydrase II. Moreover, OP-1 markedly increased the capacity of 1,25(OH)(2)D-3 to induce osteoclast-like cell formation and bone resorption in bone marrow cultures. 25 pg/ml of calcitonin significantly inhibited both OP-1- and vitamin D-3-induced TRAP-positive MNC-formation in marrow cultures,indicating that in both cases the MNC formation was calcitonin sensitive. OP-1 at 5-100 ng/ml did not have any significant effect on bone resorption as studied by pit formation assay. These studies suggest that OP-1 in concert with 1,25(OH)(2)D-3 could have an important role in bone remodeling by exhibiting its effects not only on osteoblast growth and differentiation but also on the recruitment of osteoclasts. (C) 1995 Academic Press, Inc.