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Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts

机译：双酚A减少分化并刺激破骨细胞和成骨细胞凋亡

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Aims Bisphenol A (BPA), a major component of epoxy resins used in protective coatings, is a known endocrine-disrupting chemical. BPA has the ability of binding to estrogen receptors. In the current paper, we examine the direct effects of bisphenol A on in vitro osteoclast and osteoblast culture systems. Main methods We evaluated the effects of BPA on osteoclast formation using bone marrow-derived macrophages and RAW 264.7 cells and on osteoblast differentiation using MC3T3-E1 cells. Key findings BPA significantly inhibited RANKL-induced, TRAP-positive multinucleated cell formation in bone marrow-derived macrophages and RAW 264.7 cell cultures in a dose-dependent manner (0.5 μM to 12.5 μM). We observed suppression of ERK, JNK, AKT, and p38 mitogen-activated protein kinases induced by RANKL in Western blotting after BPA treatment in RAW 264.7 cells. Furthermore, BPA suppressed Bcl-2 (anti-apoptotic) while stimulating Bax (pro-apoptotic) protein expression in RAW 264.7 cells. Bisphenol A also significantly suppressed ALP activities and bone nodule formation in MC3T3-E1 cell cultures. Specifically, the expression of Bcl-2 protein was decreased, and changes in expression of caspases 3, 8, and 9 were detected by BPA treatment in both cells. Significance We found that bisphenol A directly suppressed both osteoclastic and osteoblastic activities in vitro. Our data suggest that bisphenol A suppresses cell differentiation and survival.
机译：目标双酚A（BPA）是保护涂料中使用的环氧树脂的主要成分，是一种已知的破坏内分泌的化学物质。 BPA具有与雌激素受体结合的能力。在本文中，我们研究了双酚A对体外破骨细胞和成骨细胞培养系统的直接影响。主要方法我们使用骨髓来源的巨噬细胞和RAW 264.7细胞评估了BPA对破骨细胞形成的影响，以及使用MC3T3-E1细胞对BPA对成骨细胞分化的影响。主要发现BPA以剂量依赖性方式（0.5μM至12.5μM）显着抑制了骨髓来源的巨噬细胞和RAW 264.7细胞培养物中RANKL诱导的TRAP阳性多核细胞形成。我们观察到在BPA处理后RAW 264.7细胞中Western blotting中RANKL诱导的ERK，JNK，AKT和p38丝裂原活化蛋白激酶的抑制。此外，BPA抑制Bcl-2（抗凋亡），同时刺激RAW 264.7细胞中的Bax（促凋亡）蛋白表达。双酚A还可以显着抑制MC3T3-E1细胞培养物中的ALP活性和骨结节形成。具体而言，通过BPA处理在两个细胞中均检测到Bcl-2蛋白的表达降低，并且检测到胱天蛋白酶3、8和9的表达变化。意义我们发现双酚A在体外直接抑制破骨细胞和成骨细胞的活性。我们的数据表明双酚A抑制细胞分化和存活。

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