Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences, University of Granada, Avda. Ilustración 60, 18016 Granada, Spain.
Institute of Biosanitary Research, ibs.Granada, Avda. de Madrid 15, Pabellón de Consultas Externas, 2ª Planta, 18012 Granada, Spain.
Genes (Basel). 2024 Nov 11;15(11):1453. doi: 10.3390/genes15111453.
Bisphenol A (BPA) and its analogs (BPF, BPS, and BPAF) are recognized for inducing detrimental effects on various tissues, including bone.
The aim of this study is to investigate their impact on information and repair processes, specifically focusing on vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1), and the receptors for transforming growth factor β (TGFR1, TGFR2, and TGFR3).
Human osteoblasts isolated through primary culture from bone samples of healthy volunteers were subjected to cultivation in the presence of various dosage levels (10, 10, or 10 M) of BPA, BPF, BPS, or BPAF for 24 h. Gene expressions of RANKL, OPG, TGF-β1, TGFR1, TGFR2, TGFR3, and VEGF were analyzed by real-time polymerase chain reaction (RT-PCR). All experiments included untreated cells as controls.
Expressions of RANKL and OPG were dose-dependently downregulated by the presence of all tested bisphenols (BPs) except for BPAF, whose presence upregulated OPG expression at all three doses. TGF-β1 expression was downregulated by all BP treatments, and TGF-β1 receptor expression was also downregulated as a function of the BP and dose. VEGF expression was downregulated in the presence of BPF and BPAF at all three doses and in the presence of BPA at the two higher doses (10, and 10 M), but it was not changed by the presence of BPS at any dose.
The inhibition of both RANKL and OPG by the BPs, with a higher %inhibition of RANKL than of OPG, appears to rule out BP-induced activation of osteoclastogenesis via RANKL/RANK/OPG. Nevertheless, the effect of the BPs on the expression by osteoblasts of TGF-β1, TGF-β receptors, and VEGF indicates that these compounds can be responsible for major molecular changes in this cell population, contributing to their adverse effects on bone tissue.
双酚 A（BPA）及其类似物（BPF、BPS 和 BPAF）已被证实会对包括骨骼在内的各种组织产生有害影响。
本研究旨在探讨它们对信息和修复过程的影响，特别是针对血管内皮生长因子（VEGF）、转化生长因子β1（TGF-β1）和转化生长因子β受体（TGFR1、TGFR2 和 TGFR3）。
通过对健康志愿者骨样本进行原代培养分离出人成骨细胞，将其在不同浓度（10、10 或 10 M）的 BPA、BPF、BPS 或 BPAF 存在下培养 24 小时。通过实时聚合酶链反应（RT-PCR）分析 RANKL、OPG、TGF-β1、TGFR1、TGFR2、TGFR3 和 VEGF 的基因表达。所有实验均以未处理的细胞作为对照。
除 BPAF 外，所有测试的双酚（BP）均呈剂量依赖性地下调 RANKL 和 OPG 的表达，而 BPAF 则上调了所有三种剂量的 OPG 表达。所有 BP 处理均下调 TGF-β1 的表达，并且 TGF-β1 受体的表达也随着 BP 和剂量的变化而下调。在所有三种剂量下，BPF 和 BPAF 的存在均下调了 VEGF 的表达，而在较高的两种剂量（10 和 10 M）下，BPA 的存在也下调了 VEGF 的表达，但 BPS 的存在并未改变任何剂量下的 VEGF 表达。
BP 抑制 RANKL 和 OPG 的表达，且对 RANKL 的抑制作用高于对 OPG 的抑制作用，这似乎排除了 BP 通过 RANKL/RANK/OPG 诱导破骨细胞生成的激活。然而，BP 对成骨细胞表达 TGF-β1、TGF-β 受体和 VEGF 的影响表明，这些化合物可能导致该细胞群的主要分子变化，从而对骨组织产生不利影响。
