Low-dose exposure to triclosan disrupted osteogenic differentiation of mouse embryonic stem cells via BMP/ERK/Smad/Runx-2 signalling pathway
Low-dose exposure to triclosan disrupted osteogenic differentiation of mouse embryonic stem cells via BMP/ERK/Smad/Runx-2 signalling pathway
复制标题
低剂量三氯生暴露通过 BMP/ERK/Smad/Runx-2 信号通路破坏小鼠胚胎干细胞的成骨分化
DOI：
10.1016/j.fct.2019.02.038
复制
发表时间：
2019-05-01
影响因子：
4.3
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Cheng, Wei;Yang, Shoufei;Wang, Yan
三氯生（TCS）因其广谱抗菌活性而广泛应用于个人护理产品中。在脐带血清、羊水和胎盘中检测到TCS，引起了人们对胎儿发育风险的担忧。在本研究中，胚胎干细胞试验（EST）主要用于评价TCS对体外心脏发生和成骨的不良影响。预测TCS在心脏发生中具有弱胚胎毒性，在骨发生中具有强胚胎毒性。成骨分化的50%抑制值比心肌分化的50%抑制值低110倍，这表明骨骼系统的发育对TCS诱导的破坏更敏感。进一步探讨TCS对成骨细胞毒性作用的机制。在暴露于低剂量TCS（等于人体内暴露水平）后，观察到ESC衍生的成骨细胞钙化减少。观察到TCS特异性靶向ERK活化，而不是JNK或p38。此外，当细胞暴露于TCS时，通过BMP/ERK/Smad信号传导观察到p-Smad-1的下调以及对Runx-2和Bglap-2表达的强烈抑制。由低剂量TCS诱导的Runx-2的变化突出了探索其对骨骼发育的不利影响的特定目标。
Triclosan (TCS) has been used widely in personal care products for its broad-spectrum antimicrobial activity. The detection of TCS in the umbilical cord sera, amniotic fluid, and placenta, has raised concerns about the risk to foetal development. In the current study, the embryonic stem cells test (EST) were utilized primarily for the evaluation of the adverse effects of TCS on cardiogenesis and osteogenesis in vitro. TCS was predicted to be weakly embryotoxic in cardiogenesis and strongly embryotoxic in osteogenesis. The 50% inhibition value of osteogenic differentiation was 110 times lower than that of cardiac differentiation, which suggested that the development of the skeletal system was more sensitive to TCS-induced disruption. The mechanism through which TCS exerted toxicity on osteogenesis was studied further. Decreased calcification in ESC-derived osteoblasts was observed after exposure to TCS at a low dose, equal to the human internal exposure level. TCS was observed to specifically target ERK activation, rather than JNK or p38. Further, the downregulation of p-Smad-1, together with strong inhibition on Runx-2 and Bglap-2 expression, was observed via BMP/ERK/Smad signalling when cells were exposed to TCS. The change in Runx-2 induced by a low-dose TCS highlighted a specific target for exploring its adverse effect on skeletal development.