Cadmium exposure triggers osteoporosis in duck via P2X7/PI3K/AKT-mediated osteoblast and osteoclast differentiation
Cadmium exposure triggers osteoporosis in duck via P2X7/PI3K/AKT-mediated osteoblast and osteoclast differentiation
复制标题
镉暴露通过 P2X7/PI3K/AKT 介导的成骨细胞和破骨细胞分化引发鸭骨质疏松
DOI：
10.1016/j.scitotenv.2020.141638
复制
发表时间：
2021-01-01
影响因子：
9.8
通讯作者：
Liu, Zongping
中科院分区：
文献类型：
--
作者：
Ma, Yonggang;Ran, Di;Liu, Zongping
镉是一种常见的环境污染物，会积聚在骨骼和肾脏中，并导致严重的健康和社会问题。然而，镉对骨质疏松发生的影响及其在此过程中的作用机制尚不清楚。为了检测镉诱导的骨质疏松是否通过P2 X7/PI 3 K/AKT信号通路介导，将鸭骨髓间充质干细胞（BMSCs）和骨髓巨噬细胞（BMSCs）用镉处理5天，并将鸭胚胎用镉处理。显微CT分析表明，镉诱导的骨质疏松症发生在体内，组织病理学和免疫组化分析也表明，镉诱导骨损伤和成骨和骨吸收相关蛋白的下调。镉暴露显著抑制BMSCs和BMSCs向成骨细胞和破骨细胞的分化，促进成骨细胞和破骨细胞凋亡。镉暴露显著下调体内和体外P2 X7/PI 3 K/AKT信号通路，抑制该信号通路显著加重成骨细胞和破骨细胞的分化。镉暴露也上调OPG/RANKL比例在体内和体外，进一步抑制破骨细胞分化。这些结果表明，镉通过抑制P2 X7/PI 3 K/AKT信号通路和增加OPG/RANKL比值引起鸭骨质疏松症。这些结果建立了一个以前未知的镉诱导骨质疏松症的机制。(C)2020 Elsevier B. V.保留所有权利。
Cadmium is a common environmental pollutant that accumulates in the bone and kidneys and causes severe health and social problems. However, the effects of Cd on the occurrence of osteoporosis and its mechanism of action in this process are unclear. To test whether Cd-induced osteoporosis is mediated via P2X7/PI3K/AKT signaling, duck bone marrow mesenchymal stem cells (BMSCs) and bone marrow macrophage cells (BMMs) were treated with Cd for 5 days, and duck embryos were treated with Cd. Micro-CT analysis indicated that Cd-induced osteoporosis occurs in vivo, and histopathology and immunohistochemical analyses also revealed that Cd induced bone damage and the downregulation of osteogenic and bone resorption-related proteins. Cd exposure significantly inhibited the differentiation of BMSCs and BMMs into osteoblasts and osteoclasts in vitro, and promoted osteoblast and osteoclast apoptosis. Cd exposure significantly downregulated the P2X7/PI3K/AKT signaling pathway in vivo and in vitro, and inhibition of this signaling pathway significantly aggravated osteoblast and osteoclast differentiation. Cd exposure also upregulated the OPG/RANKL ratio in vivo and in vitro, further inhibiting osteoclast differentiation. These results demonstrate that Cd causes osteoporosis in duck by inhibiting P2X7/PI3K/AKT signaling and increasing the OPG/RANKL ratio. These results establish a previously unknown mechanism of Cd-induced osteoporosis. (C) 2020 Elsevier B.V. All rights reserved.