雌激素與雙酚 A影響軟骨細胞上金屬蛋白酶與一氧化氮表現之探討

臨床上，婦女由於雌激素在停經期減少，隨著年齡的增加，退化性關節炎患者的女性比例也隨之增高。體外實驗發現，雌激素可以影響間質金屬結合蛋白脢及金屬蛋白脢組織抑制物 1 在退化性關節炎軟骨的表現。雙酚 A 為內分泌干擾物質，干擾雌激素訊息傳遞。因此本研究使用雌激素與雙酚 A 來觀察其對於 IL-1β 誘發 SW1353 軟骨瘤細胞與人類初代軟骨細胞產生間質金屬結合蛋白酶與一氧化氮的影響，發現單獨處理高濃度雙酚 A 在會抑制 SW1353 表現一氧化氮，同時影響細胞存活度，但在低濃度下則否，此結果亦在人類初代軟骨細胞上發現。另外，實驗發現人類初代軟骨細胞中， 0.1 nM 雌激素可以有效抑制 IL-1β 產生 MMP-1 ，但於 10 nM 雌激素則相反，推論是透過影響 NF-? 羠路徑。而雙酚 A 在低濃度時會干擾 0.1 nM 雌激素的保護關節之效果。實驗結果發現 100 nM 雙酚 A 會干擾雌激素對軟骨的保護效果，同時使 NF-kappa B 活化。此外，利用液相層析法偵測血清以及關節液中雙酚 A 的濃度，發現關節液同時存在於關節置換術的關節液與血清中。根據本篇實驗總結，雙酚 A 可能影響退化性關節炎進程的因素之一，且雌激素的過量使用可能導致關節炎更為嚴重。

Regulation of matrix metalloproteinases and nitric oxide by estradiol and Bisphenol A in chondrocytes

Clinically, due to hormones changing around menopause, women have thought to have higher risk of osteoarthritis increasing with the age. In vitro studies have reported that estrogen could down-regulates the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in osteoarthritis chondrocytes. Bisphenol A is one of the endocrine-disrupting chemicals, which mimic the estrogen binding and confluence the hormone signaling in the body. Therefore, in this study we explore the effects of BPA and estradiol on the expression of MMP-1 and nitric oxide (NO) in vitro. The data shows that high concentration of BPA could reduce NO production, and could suppress the cell viability in SW1353 chondrosarcoma cell line and in human primary chondrocyte. But low concentration of BPA couldn’t exhibit this effect. However, in human primary chondrocyte, 0.1 nM estrogen could effectively reduce MMP-1 production that stimulation by IL-1 beta??, but 10 nM estrogen could reverse the effect, suggesting that through the NF-kappa B pathway. The present study also shows that 100 nM BPA could interfere with the protective effect of estrogen on the cartilage, and could stimulate NF-kappa B activation. This study also detect the concentration of BPA in serum and in synovial fluid by HPLC-UV, finding that BPA both exist in serum and synovial fluid of the patient who undergoes the knee replacement arthroplasty. In conclusion, BPA would be one of the factors improving the progression of osteoarthritis; otherwise, high dose of estrogen would cause the high severity of osteoarthritis.