Genistein reduces the production of proinflammatory molecules in human chondrocytes

Hooshmand, Shirin; Soung, Do Y.; Lucas, Edralin A.; Madihally, Sundar V.; Levenson, Cathy W.; Arjmandi, Bahram H.

doi:10.1016/j.jnutbio.2006.11.006

« Previous Next »The Journal of Nutritional Biochemistry
Volume 18, Issue 9 , Pages 609-614, September 2007

Genistein reduces the production of proinflammatory molecules in human chondrocytes

Shirin Hooshmand
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306-1493, USA
Do Y. Soung
- Center of Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA
Edralin A. Lucas
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA
Sundar V. Madihally
- School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, USA
Cathy W. Levenson
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306-1493, USA
Bahram H. Arjmandi
- Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee, FL 32306-1493, USA
- Corresponding author. Tel.: +1 850 644 1828; fax: +1 850 645 5000.

Received 9 August 2006; received in revised form 2 November 2006; accepted 9 November 2006. published online 19 March 2007.

Abstract

Previously, we reported that cartilage is an estrogen receptor (ER) positive tissue and that mRNA levels of ERβ 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 ER 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 ERβ, in inhibiting the lipopolysaccharide (LPS)-stimulated cyclooxygenase (COX)-2 in chondrocytes. Primary cultures of normal human chondrocytes were treated with three levels of genistein (0, 50, and 100 μM). After 1 h, the genistein-treated cells were stimulated by 1 μg/ml LPS for 24 h. Cells were then harvested, and the cytosolic fraction was isolated for assessment of COX-1 and COX-2 protein levels using Western analysis. Nitric oxide (NO), interleukin-I beta (IL-1β), and human cartilage glycoprotein 39 (YKL-40) production was also measured in cell supernatants. NO and IL-1β were measured as markers of inflammation, and YKL-40 was assessed as a marker of cartilage catabolism. Genistein had no significant effect on either YKL-40 or IL-1β 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. The ability of genistein to suppress COX-2 but not COX-1 is advantageous because suppressing COX-2 can lead to suppression of proinflammatory molecules. Although genistein suppresses COX-2 production, it does not affect the production of COX-1 enzyme, which is responsible for releasing prostaglandins involved in cellular house-keeping functions such as the maintenance of gastrointestinal integrity and vascular homeostasis.

Keywords: Isoflavones, Inflammation, SERM, Lipopolysaccharide