Calcium relieves fluoride-induced bone damage through the PI3K/AKT pathway
| Autor: | Jundong Wang, Xiaofang Cheng, Huimiao Xu, Zipeng Yan, Jiarong Yang, Haili Ma, Ram Kumar Manthari, Mohammad Mehdi Ommati, Jinming Wang, Yangfei Zhao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty chemistry.chemical_element Apoptosis FOXO1 Calcium Bone and Bones Rats Sprague-Dawley Fluorides Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Sodium fluoride medicine Animals Protein Glutamine gamma Glutamyltransferase 2 Protein kinase B PI3K/AKT/mTOR pathway Calcium metabolism Akt/PKB signaling pathway General Medicine Rats 030104 developmental biology Endocrinology chemistry 030220 oncology & carcinogenesis Signal transduction Proto-Oncogene Proteins c-akt Fluoride Poisoning Signal Transduction Food Science |
| Zdroj: | Food & Function. 11:1155-1164 |
| ISSN: | 2042-650X 2042-6496 |
| DOI: | 10.1039/c9fo02491c |
| Popis: | Bone is the main target of fluorosis, and it has been perfectly elaborated that a moderate dosage of calcium (Ca) can alleviate bone fluorosis. However, whether Ca can alleviate fluorosis through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway has not yet been reported. Hence, we evaluated the histopathological structure, the imbalance of the biochemical index of bone metabolism, and the expression levels of PI3K/AKT apoptosis signaling pathway-related genes in rats treated with sodium fluoride (NaF, F) and/or calcium carbonate (CaCO3) for 120 days. Our results suggest that 100 mg L-1 NaF induced histopathological injury as alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (StrACP) activity increased, with a decrease in the serum Ca levels (p < 0.05). Moreover, the results of qRT-PCR and western blotting showed that F increased the expression levels of transglutaminase 2 (TGM2), focal adhesion kinase (FAK), PI3K, AKT, forkhead box O1 (Foxo1), Bcl-2 interacting mediator of cell death (BIM), Bcl2-associated x protein (Bax) and Caspase 3 (p < 0.05, p < 0.01). It also decreased the expression of AnnexinA5 (Anxa5), 3'-phosphoinositide-dependent kinase 1 (PDK1) and B-cell lymphoma-2 (Bcl-2) (p < 0.05, p < 0.01), which finally activated the PI3K/AKT pathway. On the other hand, CaCO3 supplementation reversed the histopathological injury along with the levels of ALP, StrACP and serum Ca, alleviating the gene expression levels of PI3K/AKT pathway-related markers. Altogether, we can conclude that CaCO3 supplementation mitigated F-induced bone damage via the PI3K/AKT signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|