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 AlCl 3 (AlCl 3 treated group, AG) in drinking water for 120days; osteoblasts were treated with AlCl 3 (0.12mg/mL) and/or TGF-β1 (4.5ng/mL) for 24h. We found that AlCl 3 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-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 AlCl 3 on 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 AlCl 3 induces bone impairment through inactivation of TGF-β1/Smad signaling pathway.
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There is increased risk of osteoporosis and low bone mineral density during Al exposure because of disruption of bone formation, and inhibition of osteoblast proliferation, differentiation and mineralization.
“There is increased risk of osteoporosis and low bone mineral density during Al exposure (Cao et al., 2016; Sun et al., 2016) because of disruption of bone formation, and inhibition of osteoblast proliferation, differentiation and mineralization (Li et al., 2012, 2016; Cao et al., 2016; Sun et al., 2016; Yang et al., 2016; Zhu et al., 2016b; Song et al., 2017; Sun et al., 2017; Huang et al., 2017).”
From Aluminium toxicosis: a review of toxic actions and effects (2019) · cites this paper as Sun et al., 2016
Cites
Transforming Growth Factor-β1 to the Bone
Janssens, K., ten Dijke, P., Janssens, S., & Van Hul, W. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0001 · Cited by 710 · see citing works
Cao, Z., Fu, Y., Sun, X., Zhang, Q., Xu, F., & Li, Y. (2016) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2015.11.023 · Cited by 26 · see citing works
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Aluminium toxicosis: a review of toxic actions and effects
Igbokwe, I. O., Igwenagu, E., & Igbokwe, N. A. (2019) · Interdisciplinary Toxicology · doi:10.2478/intox-2019-0007 · Cited by 395 · see citing works
“…predisposing cells to or causing genotoxicity (Pogue and Lukiw, 2016) and thus Al exposure may lead to reduction of cell proliferation and differentiation (Nam et al., 2014, 2016; Sun et al., 2015; Cao et al., 2016; Li et al., 2016; Yang et al., 2016; Sun et al., 2016, 2017; Huang et al., 2017).”
BackgroundInfluentialWang, X., Chen, B., Sun, J., Jiang, Y., Zhang, H., Zhang, P., Fei, B., & Xu, Y. (2018) · Metabolism · doi:10.1016/j.metabol.2018.01.005 · Cited by 113 · see citing works
- Authors
- Sun, X., Liu, J., Zhuang, C., Yang, X., Han, Y., Shao, B., Song, M., Li, Y., & Zhu, Y.
- Affiliations
- Northeast Agricultural University (CN)
- Police Dog Technical School (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Corresponding author
- Li, Yanfei
- Zhu, Yanzhu
- ORCID
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 371
- Pages
- 49-57
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W2528071705
- Cited by
- 28
- References
- 2
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 1
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation Project (31372496, 31302147)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- aluminum chloride, aluminum toxicity, osteoporosis, TGF-β1/Smad signaling, osteoblasts, bone mineral density, oxidative stress, Smad7, TGF-β1, bone turnover markers
- MeSH terms
- Aluminum Chloride, Alkaline Phosphatase, Animals, Antioxidants, Bone Diseases, Bone Resorption, Chlorides, Femur, Male, Osteoblasts, Signal Transduction, Bone Density, Gene Expression, Rats, Sprague-Dawley, Aluminum Compounds, Collagen Type I, Rats, Smad Proteins, Transforming Growth Factor beta1, Drinking Water
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