Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
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.
绝经后雌激素 (E2) 流失使老年女性患骨关节炎 (OA) 的风险增加。研究表明，E2 可抑制核因子 (NF)-kappaB 的活性，而关节炎发病机制中 NF-kappaB 的活性会增加。其他研究表明，外源性 E2 可降低 OA 软骨细胞中基质金属蛋白酶 (MMPs) 的表达，并减轻 OA 的发病机制。双酚 A (BPA) 是一种重要的工业材料，也是一种内分泌干扰化学物质 (EDC)，可与 E2 受体结合并中断激素信号。目前尚不清楚 BPA 如何影响 E2 功能以及影响 E2 介导的 OA 保护作用。在这项研究中，我们研究了 E2 和 BPA 对软骨肉瘤 SW1353 细胞和原代人骨性关节炎软骨细胞中一氧化氮 (NO) 产生、NF-kappaB 激活和 MMP-1 表达的影响。在测试的化学物质中，BPA 降低了软骨肉瘤细胞的 NO 产生和细胞活力，但对骨性关节炎软骨细胞几乎没有影响。通过 HPLC-UV，我们观察到 OA 患者血清和滑液中的 BPA。在原代软骨细胞中，适量浓度的 E2 可降低白细胞介素 (IL)-1beta 依赖性 NF-kappaB 激活和 MMP-1 表达。BPA 以浓度依赖的方式拮抗了 E2 的这些保护作用。总之，BPA 干扰了软骨细胞中 E2 的功能，可能会促进 OA 的发生。
