Bisphenol-A interferes with estradiol-mediated protection in osteoarthritic chondrocytes

Toxicol Lett. 2010 Oct 5;198(2):127-33. doi: 10.1016/j.toxlet.2010.06.007. Epub 2010 Jun 30.


Aged women have a higher risk of osteoarthritis (OA) due to estrogen (E2) loss at menopause. Studies suggested that E2 inhibits nuclear factor (NF)-kappaB activity which is increased in arthritis pathogenesis. Other studies revealed that external E2 reduces the expression of matrix metalloproteinases (MMPs) in osteoarthritic chondrocytes, and attenuates the pathogenesis of OA. Bisphenol-A (BPA) is an important industrial material, and an endocrine-disrupting chemical (EDC) that binds E2 receptors and interrupts the hormone signaling. It is unknown how BPA affects E2 functions and influences E2-mediated protections in OA. In this study, we investigated the effects of E2 and BPA on nitric oxide (NO) production, NF-kappaB activation, and MMP-1 expression in chondrosarcoma SW1353 cells and primary human osteoarthritic chondrocytes. Among the tested chemicals, BPA reduced NO production and cell viability of chondrosarcoma cells, but had little effects on osteoarthritic chondrocytes. Using HPLC-UV, we observed BPA in the serum and synovial fluid of OA patients. In primary chondrocytes, modest concentrations of E2 reduced interleukin (IL)-1beta-dependent NF-kappaB activation and MMP-1 expression. BPA antagonized these protective effects of E2 in a concentration-dependent manner. In conclusion, BPA interferes with E2's functions in chondrocytes and may promote OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Blotting, Western
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Endocrine Disruptors / toxicity*
  • Estradiol / pharmacology*
  • Estradiol / physiology
  • Estrogen Receptor beta / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Matrix Metalloproteinase 1 / biosynthesis
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Osteoarthritis, Knee / blood
  • Osteoarthritis, Knee / pathology*
  • Osteoarthritis, Knee / prevention & control
  • Phenols / blood
  • Phenols / toxicity*
  • Protein Binding
  • Synovial Fluid / metabolism


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Estrogen Receptor beta
  • Interleukin-1
  • NF-kappa B
  • Phenols
  • Nitric Oxide
  • Estradiol
  • Matrix Metalloproteinase 1
  • bisphenol A