BINDING AND BIOEFFECTS OF IPRIFLAVONE ON A HUMAN PREOSTEOCLASTIC CELL-LINE

Ipriflavone, a synthetic isoflavone derivative, reduces bone resorptio n by inhibiting osteoclasts activity. In order to evaluate the role of Ipriflavone on osteoclast growth and differentiation we tested Iprifl avone and its four ''in vivo'' main metabolites (Metabolites I, II, II I, and V) on a clonal population of human osteoclast precursor cells ( FLG 29.1). Pharmacological doses of Ipriflavone and Metabolite III wer e able to inhibit cell proliferation and interleukin 6 release In cocu ltures of FLG 29.1 cells and osteoblastic (Saos-2) cells Ipriflavone a t 1 mu M dose inhibited the adhesion of FLG 29.1 cells to the osteobla stic monolayer and reduced the immunocytochemical reaction of the vitr onectin receptor. Binding studies with tritiated Ipriflavone showed th e presence of a single specific binding site, with a Kd of about 70 nM and a binding capacity of 8 fmol/10(6) cells. These results demonstra te a direct effect of Ipriflavone and of Metabolite III on the human o steoclast precursor cell line FLG 29.1. (C) 1994 Academic Press, Inc.