EFFECTS OF IPRIFLAVONE AND ITS METABOLITES ON HUMAN ARTICULAR CHONDROCYTES CULTIVATED IN CLUSTERS

Ipriflavone (IF) is an isoflavone derivative that was suggested to hav e bone-sparing effects in post-menopausal and senile osteoporosis. A m oderate stimulatory effect of IP and its metabolites on proliferation of osteoblastic cells was reported in rat osteoblastic osteosarcoma ce ll line. We investigated the effects of different concentrations (0, 1 , 10 and 100 mu g/ml) of IP and its metabolites (MET I, II, III and V) on the incorporation of [H-3]thymidine and production of proteoglycan s (PG) and type II collagen (COL II) by human articular chondrocytes d uring a 12-day period, in a three-dimensional chondrocyte culture mode l. [H-3]thymidine uptake was measured in chondrocyte clusters, and spe cific PG and COL II radioimmunoassays were performed every 4 days on t he culture medium and cell clusters. Incubation with LP or its metabol ites did not affect [H-3]thymidine uptake regardless of the dose. PG r eleased into the culture medium and PG cluster content rose significan tly (P < 0.025) in presence of LP (1, 10 and 100 mu g/ml). MET I incre ased PG release in culture medium (10 and 100 mu g/ml) and PG cluster content (100 mu g/ml). MET II has no effect on PG production. MET III increased PG in culture medium (100 mu g/ml) but did not influence PG cluster content while MET V (100 mu g/ml) increased both PG release in culture medium and PG cluster content. COL II release in culture medi um and COL II cluster content were significantly (P < 0.025) increased in presence of IP (10 and 100 mu g/ml), MET III (1, 10 and 100 mu g/m l) or MET V (100 mu g/ml). MET I and II did not significantly affect C OL II production.