Effects of Ipriflavone and its metabolites on human articular chondrocytes cultivated in clusters

Ipriflavone (IF) is an isoflavone derivative that was suggested to have bone-sparing effects in post-menopausal and senile osteoporosis. A moderate stimulatory effect of IP and its metabolites on proliferation of osteoblastic cells was reported in rat osteoblastic osteosarcoma cell 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 proteoglycans (PG) and type II collagen (COL II) by human articular chondrocytes during a 12-day period, in a three-dimensional chondrocyte culture model. [H-3]thymidine uptake was measured in chondrocyte clusters, and specific PG and COL II radioimmunoassays were performed every 4 days on the culture medium and cell clusters. Incubation with LP or its metabolites did not affect [H-3]thymidine uptake regardless of the dose. PG released into the culture medium and PG cluster content rose significantly (P < 0.025) in presence of LP (1, 10 and 100 mu g/ml). MET I increased 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 medium 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/ml) or MET V (100 mu g/ml). MET I and II did not significantly affect COL II production.