Aluminum trichloride induces bone impairment through TGF-ß1/Smad signaling pathway.
Toxicology
; 371: 49-57, 2016 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-27720690
ABSTRACT
Aluminum (Al) is recognized worldwide as serious inorganic contaminants. Exposure to Al is associated with low BMD and an increased risk of osteoporosis. However, the precise molecular mechanisms remains unclear. Thus, in this study, rats were orally exposed to 0 (control group, CG) and 0.4g/L AlCl3 (AlCl3 treated group, AG) in drinking water for 120days; osteoblasts were treated with AlCl3 (0.12mg/mL) and/or TGF-ß1 (4.5ng/mL) for 24h. We found that AlCl3 decreased the BMD, damaged femoral ultrastructure, decreased the activities of GSH-Px and SOD, and increased the levels of ROS and MDA in bone, decreased the activity of B-ALP and content of PINP, and increased the activity of TRACP-5b and content of NTX-I in serum, decreased mRNA expressions of TGF-ß1, TßRI, TßRII and Smad4, protein expressions of TGF-ß1, p-Smad2/3 and Smad2/3/4 complex, and increased Smad7 mRNA expression in bone and in osteoblasts. Moreover, we found exogenous TGF-ß1 application reversed the inhibitory effect of AlCl3 on osteoblasts activity by activating the TGF-ß1/Smad signaling pathway and increasing the mRNA expressions of ALP and Col I in osteoblasts. These results demonstrate that AlCl3 induces bone impairment through inactivation of TGF-ß1/Smad signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Ósseas
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Cloretos
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Compostos de Alumínio
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Proteínas Smad
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Fator de Crescimento Transformador beta1
Limite:
Animals
Idioma:
En
Revista:
Toxicology
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China