School of Public Health, Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou 510515, PR China.
School of Public Health, Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, Southern Medical University, Guangzhou 510515, PR China.
Toxicol Lett. 2022 Aug 15;367:9-18. doi: 10.1016/j.toxlet.2022.07.005. Epub 2022 Jul 14.
Cadmium (Cd)-induced bone damage may be mediated through activating osteoclastogenesis. However, the underlying mechanism is unknown. The purpose of this study was to explore the effect and possible mechanism of CdCl-induced osteoclastogenesis in RAW264.7 cells. We found that a low concentration of CdCl (0.025 and 0.050 µM) did not affect the viability of RAW264.7 cells, but promoted osteoclastogenesis. A low concentration of CdCl increased the mRNA and protein expression of osteoclastogenesis-related genes. TRAP staining and transmission electron microscopy (TEM) also demonstrated that CdCl promoted osteoclastogenesis. A low concentration of CdCl upregulated the levels of LC3-II and Beclin-1, and decreased p62 expression. TEM showed relatively abundant autophagic vacuoles (autophagosomes) after CdCl exposure. A low concentration of CdCl downregulated the expression levels of Mtor and p70S6K1, and the relative protein expression ratios of p-mTOR/mTOR and p-p70S6K1/p70S6K1. When cells were treated with the autophagy inhibitor chloroquine (CQ) or mTOR activator MHY1485 combined with CdCl, the expressions of osteoclastogenesis related-genes were decreased and autophagy was attenuated compared with cells treated with CdCl alone. Deficiencies in autophagosomes and osteoclasts were also observed. Taken together, the results indicate that a low concentration of CdCl promotes osteoclastogenesis by enhancing autophagy via inhibiting the mTOR/p70S6K1 signaling pathway.
镉（Cd）诱导的骨损伤可能通过激活破骨细胞发生来介导。然而，其潜在机制尚不清楚。本研究旨在探讨 CdCl 在 RAW264.7 细胞中诱导破骨细胞发生的作用及其可能的机制。我们发现，低浓度的 CdCl（0.025 和 0.050 μM）不会影响 RAW264.7 细胞的活力，但会促进破骨细胞发生。低浓度的 CdCl 增加了破骨细胞发生相关基因的 mRNA 和蛋白表达。TRAP 染色和透射电子显微镜（TEM）也表明 CdCl 促进了破骨细胞发生。低浓度的 CdCl 上调了 LC3-II 和 Beclin-1 的水平，并降低了 p62 的表达。TEM 显示 CdCl 暴露后相对丰富的自噬小体（自噬体）。低浓度的 CdCl 下调了 Mtor 和 p70S6K1 的表达水平，以及 p-mTOR/mTOR 和 p-p70S6K1/p70S6K1 的相对蛋白表达比值。当用自噬抑制剂氯喹（CQ）或 mTOR 激活剂 MHY1485 联合 CdCl 处理细胞时，与单独用 CdCl 处理的细胞相比，破骨细胞发生相关基因的表达降低，自噬减弱。还观察到自噬小体和破骨细胞的缺陷。总之，结果表明，低浓度的 CdCl 通过抑制 mTOR/p70S6K1 信号通路增强自噬来促进破骨细胞发生。
