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- Title
Cadmium accelerates autophagy of osteocytes by inhibiting the PI3K/AKT/mTOR signaling pathway.
- Authors
Song, Ruilong; He, Shuangjiang; Cao, Ying; Lu, Yicheng; Peng, Yunwen; Zou, Hui; Tong, Xishuai; Ran, Di; Ma, Yonggang; Liu, Zongping
- Abstract
Cadmium (Cd) can damage bone cells and cause osteoporosis. Osteocytes are the most numerous bone cells and also important target cells for Cd‐induced osteotoxic damage. Autophagy plays important role in the progression of osteoporosis. However, osteocyte autophagy in Cd‐induced bone injury is not well characterized. Thus, we established a Cd‐induced bone injury model in BALB/c mice and a cellular damage model in MLO‐Y4 cells. Aqueous Cd exposure for 16 months showed an increase in plasma alkaline phosphatase (ALP) activity and increase in urine calcium (Ca) and phosphorus (P) concentrations in vivo. Moreover, expression level of autophagy‐related microtubule‐associated protein 1A/1B‐light chain 3 II (LC3II) and autophagy‐related 5 (ATG5) proteins were induced, and the expression of sequestosome‐1 (p62) was reduced, along with Cd‐induced trabecular bone damage. In addition, Cd inhibited the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3‐kinase (PI3K). In vitro, 80 μM Cd concentrations exposure upregulated LC3II protein expression, and downregulated of p62 protein expression. Similarly, we found that treatment with 80 μM Cd resulted in a reduction in the phosphorylation levels of mTOR, AKT, and PI3K. Further experiments revealed that addition of rapamycin, an autophagy inducer, enhanced autophagy and alleviated the Cd‐induced damage to MLO‐Y4 cells. The findings of our study reveal for the first time that Cd causes damage to both bone and osteocytes, as well as induces autophagy in osteocytes and inhibits PI3K/AKT/mTOR signaling, which could be a protective mechanism against Cd‐induced bone injury.
- Subjects
OSTEOCYTES; PROTEIN kinase B; AUTOPHAGY; ALKALINE phosphatase; CELLULAR signal transduction; PHOSPHATIDYLINOSITOL 3-kinases
- Publication
Environmental Toxicology, 2023, Vol 38, Issue 8, p1980
- ISSN
1520-4081
- Publication type
Article
- DOI
10.1002/tox.23823