Loading...
Thumbnail Image
Publication

Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes

Hooshmand-yazdi, Shirin
Abstract
Previously, we reported that cartilage is an estrogen receptor (ER) positive tissue and that mRNA levels of ER increase in postmenopausal women with osteoarthritis. Based on our findings and those of other investigators, we hypothesized that local rather than circulating estrogen levels negatively affect chondrocyte metabolism and that selective estrogen receptor modulators (SERM) augment cartilage health. To test the latter part of our hypothesis, we explored the role of genistein, a naturally occurring SERM with high affinity to bind ER, in inhibiting the lipopolysaccharide (LPS)-stimulated cyclooxygenase (COX)-2 but not COX-1 in human chondrocytes (HCH). Cells (PromoCell, Germany) were treated with three levels of genistein (0, 50, and 100 ?M). After one hour, the genistein-treated cells were stimulated by one μg/mL LPS for six hours. Cells were then harvested and the cytosolic fraction was isolated for assessing COX-1 and COX-2 protein levels using Western blot technique. Nitric oxide (NO), interleukin-I Beta (IL-1?), and YKL-40 productions were also measured in cell culture supernatants. NO, and IL-1? were measured as markers of inflammation and YKL-40 was assessed as a marker of cartilage catabolism. Interestingly, LG50 was more effective in reducing NO production than LG100 (42% vs. 28%) in comparison with LPS-treatred control cells. Genistein had no significant effect on either YKL-40 or IL-1? levels. Our data indicate that the LPS-stimulated increases in COX-2 protein level and NO in supernatant are reduced by pretreatment of genistein, whereas COX-1 protein level is not affected by genistein.
Date
2006-05-01
Collections