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

Abstract

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, 17beta-estradiol, or 5 microg/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 17beta-estradiol. Although insulin raised the sodium [35S]sulfate uptake significantly, different concentrations of daidzein, genistein, or 17beta-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 17beta-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.

Biphasic positive effect of formononetin on metabolic activity of human normal and osteoarthritic subchondral osteoblasts

“…Furthermore, it seems that phytoestrogen has an effect on preserving bone volume in the absence of estrogen [34,35]. Also, the phytoestrogens daidzein and genistein but not by 17β-estradiol enhance the insulin-stimulated glycosaminoglycan synthesis in articular chondrocytes [36]. Sanchez et al have shown that OA osteoblasts in monolayer increased glycosaminoglycan release from cartilage explants, whereas normal cells did not [37].…”

Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes

“…5,18,19) Dong et al 20) have reported that bavachin, a phytoestrogen purified from natural herbal plants such as Psoraleae corylifoliae 21) and Piper longum, 22) has estrogen-like activity in estrogen-receptor-positive human breast adenocarcinoma MCF-7/BOS cells. Therefore, we hypothesized that bavachin may have chondroprotective effects as a result of anabolic or anti-catabolic activity in articular cartilage.…”

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage

“…Although the effect of phytoestrogens, especially genistein, on the extracellular cartilage matrix has been discussed in the literature, the data are not consistent. An in vitro study found that articular chondrocyte glycosaminoglycans (GAG) synthesis was significantly diminished following incubation with high doses of genistein (10 -5 -10 -4 mol/L) but that the level of sulfate npg incorporation was not affected [1] . Nevertheless, Hooshmand et al found that high doses of genistein (10 -5 -10 -4 mol/L) could suppress the increased levels of YKL-40 (a marker of cartilage glycoprotein degradation) in chondrocyte supernatant that is induced by LPS treatment [15] .…”

“…OA is a degenerative disease characterized by the loss of collagens and proteoglycans as the main structural molecules of articular cartilage [1] . Epidemiological studies have shown that the prevalence and incidence of OA increase after menopause and that OA symptoms are more severe in postmenopausal women than in men [2][3][4] , which suggests a link between OA and estrogen.…”