Low-dose cadmium exposure promotes osteoclastogenesis by enhancing autophagy via inhibiting the mTOR/p70S6K1 signaling pathway. (15th August 2022)

• Record Type: Journal Article
• Authors: Wang, Zhaojie; Li, Dongli; Mo, Lijun; Liang, Shujun; Liao, Xuemei; Guo, Sihui; Yang, Xingfen; Wei, Qinzhi
• Is Part Of: Toxicology letters. Volume 367(2022)
• Page Start: 9
• Page End: 18
• Publication Date: 2022-08-15
• Subjects: TRAP, tartrate resistant acid phosphatase -- Rank, receptor activator of nuclear factor-kappaB -- Ctsk, cathepsin K -- Map1lc3, microtubule-associated protein 1 light chain 3 -- p62, sequestosome 1 -- Becn1, beclin 1 -- Mtor, mechanistic target of rapamycin kinase -- p70S6K1, ribosomal protein S6 kinase, polypeptide 1 -- Gapdh, glyceraldehyde-3-phosphate dehydrogenase; Cadmium -- Osteoclastogenesis -- MTOR -- Autophagy; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2022.07.005
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: 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 CdCl2 -induced osteoclastogenesis in RAW264.7 cells. We found that a low concentration of CdCl2 (0.025 and 0.050 µM) did not affect the viability of RAW264.7 cells, but promoted osteoclastogenesis. A low concentration of CdCl2 increased the mRNA and protein expression of osteoclastogenesis-related genes. TRAP staining and transmission electron microscopy (TEM) also demonstrated that CdCl2 promoted osteoclastogenesis. A low concentration of CdCl2 upregulated the levels of LC3-II and Beclin-1, and decreased p62 expression. TEM showed relatively abundant autophagic vacuoles (autophagosomes) after CdCl2 exposure. A low concentration of CdCl2 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 CdCl2, the expressions of osteoclastogenesis related-genes were decreased and autophagy was attenuated compared with cells treated with CdCl2 alone. Deficiencies in autophagosomes and osteoclasts were also observed. Taken together, the results indicate that a low concentration of CdCl2 promotes osteoclastogenesis by enhancing autophagy via inhibiting the mTOR/p70S6K1 signaling pathway. Highlights: CdCl2 promotes RANKL-induced osteoclastogenesis in RAW264.7 cells by enhancing autophagy. CdCl2 inhibites the activities of mTOR and p70S6K1 in RANKL-induced osteoclastogenesis of RAW264.7 cells. mTOR-mediated autophagy is involved in CdCl2 -induced osteoclastogenesis.