The phytoestrogens daidzein and genistein enhance the insulin-stimulated sulfate uptake in articular chondrocytes.

Clinical observations have suggested a relationship between osteoarthritis and a changed estrogen metabolism in menopausal women. Phytoestrogens have been shown to ameliorate various menopausal symptoms. Proteoglycans (PG) consisting of low and high sulfated glycosaminoglycans (GAG) are the main components of articular cartilage matrix, and their synthesis is increased by insulin in growth plate cartilage. We have investigated whether GAG synthesis and sodium [³⁵S]sulfate incorporation in female bovine articular chondrocytes are affected by daidzein, genistein, and/or insulin. For comparative purposes, estradiol incubations were performed. Articular chondrocytes were cultured in monolayers at 5% O₂ and 5% CO₂ in medium containing serum for 7 days followed by the addition of 10⁻¹¹ M–10⁻⁴ M daidzein, genistein, 17β-estradiol, or 5 μg/ml insulin in a serum-free culture phase of 2 days. Photometrically analyzed GAG synthesis was significantly suppressed by high doses (10⁻⁵ M–10⁻⁴ M) of daidzein, genistein, and 17β-estradiol. Although insulin raised the sodium [³⁵S]sulfate uptake significantly, different concentrations of daidzein, genistein, or 17β-estradiol showed no significant effects. However, the stimulating effect of insulin on sulfate incorporation was enhanced significantly after preincubation of cells with 10⁻¹¹ M–10⁻⁵ M daidzein or 10⁻⁹ M–10⁻⁵ M genistein but not by 17β-estradiol. In view of the risks of long-term estrogen replacement therapy, further experiments should clarify the potential benefit of phytoestrogens and insulin in articular cartilage metabolism. [ABSTRACT FROM AUTHOR]