title: Aluminum trichloride induces bone impairment through TGF-β1/Smad signaling pathway.
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(AlCl3treated group, AG) in drinking water for 120days; osteoblasts were treated with AlCl3(0.12mg/mL) and/or TGF-β1 (4.5ng/mL) for 24h. We found that AlCl3decreased 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-β1, TβRI, TβRII and Smad4, protein expressions of TGF-β1, p-Smad2/3 and Smad2/3/4 complex, and increased Smad7 mRNA expression in bone and in osteoblasts. Moreover, we found exogenous TGF-β1 application reversed the inhibitory effect of AlCl3on osteoblasts activity by activating the TGF-β1/Smad signaling pathway and increasing the mRNA expressions of ALP and Col I in osteoblasts. These results demonstrate that AlCl3induces bone impairment through inactivation of TGF-β1/Smad signaling pathway.
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China; College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Police Dog Technical School of Ministry of Public Security, Shenyang 110034, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhuang
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shao
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. Electronic address: liyanfei@neau.edu.cn.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Special Animal and Plant Sciences of Chinese Academy of Agricultural Sciences, Changchun 130112, China. Electronic address: zhuyanzhu@caas.cn.
authors.forename: Yanzhu
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced*; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D060766:Drinking Water; D005269:Femur / Q000187:drug effects / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000187:drug effects* / Q000494:pharmacology
chemical_list: D017607:Aluminum Compounds; D000975:Antioxidants; D002712:Chlorides; D024042:Collagen Type I; D060766:Drinking Water; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D000077410:Aluminum Chloride; D000469:Alkaline Phosphatase
keywords: Aluminum trichloride; Bone formation and resorption; Osteoblasts; Oxidative stress; TGF-β1/Smad signaling pathway