Calcium relieves fluoride-induced bone damage through the PI3K/AKT pathway

• Published in: Food & function 2020-01, Vol.11 (1), p.1155-1164
• Main Authors: Wang, Jinming, Xu, Huimiao, Cheng, Xiaofang, Yang, Jiarong, Yan, Zipeng, Ma, Haili, Zhao, Yangfei, Ommati, Mohammad Mehdi, Manthari, Ram Kumar, Wang, Jundong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; AKT protein; Alkaline phosphatase; Apoptosis; BAX protein; Bcl-2 protein; Bcl-x protein; BIM protein; Bone turnover; Calcium; Calcium carbonate; Calcium fluoride; Caspase-3; Cell death; Damage; Fluorides; Fluorosis; Focal adhesion kinase; Forkhead protein; FOXO1 protein; Gene expression; Kinases; Lymphocytes B; Lymphoma; Metabolism; Phosphatase; Proteins; Signal transduction; Signaling; Sodium fluoride; Supplements; Transglutaminase 2; Western blotting
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo02491c

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 (CaCO 3 ) 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, CaCO 3 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 CaCO 3 supplementation mitigated F-induced bone damage via the PI3K/AKT signaling pathway. Bone is the main target of fluorosis, and it has been perfectly elaborated that a moderate dosage of calcium (Ca) can alleviate bone fluorosis.