Hagiwara Hiromi, Sugizaki Toshinori, Tsukamoto Yu, Senoh Emi, Goto Tadashi, Ishihara Yoko
Department of Biomedical Engineering, Toin University of Yokohama, 1614 Kurogane-cho, Aoba-ku, Yokohama 225-8502, Japan.
Toxicol Lett. 2008 Sep;181(1):13-8. doi: 10.1016/j.toxlet.2008.06.863. Epub 2008 Jun 26.
Alkylphenols are endocrine disruptors that show estrogen-like effects in various wildlife species. However, little information is available about the action of these chemicals on bone metabolism. We investigated the effects of alkylphenols, such as nonylphenol (NP) and octylphenol (OP), on the formation of bone using several culture systems for osteoclasts and osteoblasts, as well as in vivo experiments. NP and OP dose-dependently inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells (osteoclasts) in cocultures of mouse spleen cells or mouse bone marrow cells with ST2 cells. However, beta-estradiol at 10(-9)M to 10(-6)M did not affect this process. In contrast, neither compound affected the proliferation and differentiation of rat calvarial osteoblast-like cells (ROB cells). When NP or OP (0.1mg/kg body weight) was administered subcutaneously to pregnant mice at 10 days, 12 days and 14 days post-coitus, fetuses at 17.5 days post-coitus showed stimulation of sternebrae bone calcification. Our findings suggest that alkylphenols have critical effects on the formation of bone by non-estrogenic effects.
烷基酚是内分泌干扰物,在多种野生动物物种中表现出类似雌激素的作用。然而,关于这些化学物质对骨代谢作用的信息却很少。我们使用几种破骨细胞和成骨细胞培养系统以及体内实验,研究了壬基酚(NP)和辛基酚(OP)等烷基酚对骨形成的影响。在小鼠脾细胞或小鼠骨髓细胞与ST2细胞的共培养中,NP和OP呈剂量依赖性地抑制抗酒石酸酸性磷酸酶阳性多核细胞(破骨细胞)的形成。然而,10^(-9)M至10^(-6)M的β-雌二醇对此过程没有影响。相反,这两种化合物均未影响大鼠颅骨成骨样细胞(ROB细胞)的增殖和分化。当在交配后第10天、12天和14天对怀孕小鼠皮下注射NP或OP(0.1mg/kg体重)时,交配后17.5天的胎儿胸骨骨钙化受到刺激。我们的研究结果表明,烷基酚通过非雌激素作用对骨形成具有关键影响。