Aluminum trichloride induces bone impairment through TGF-β1/Smad signaling pathway

Sun, Xudong; Liu, Jianyu; Zhuang, Cuicui; Yang, Xu; Han, Yaling; Lei, Lei; Song, Miao; Li, Yanfei; Zhu, Yanzhu

doi:10.1016/j.tox.2016.10.002

Cited by 25 publications

(19 citation statements)

References 45 publications

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“…The TGF-β 1 and BMP-2 mRNA expressions have been decreased in vivo by Al (Li et al, 2016). The TGF-β 1 mRNA expressions have been decreased in vitro by Al (Sun et al, 2016a). The in vitro experiment with BMP-2 has not been reported.…”

Section: Introductionmentioning

confidence: 90%

“…The rat femora has been impaired by AlCl 3 through inhibiting the Wnt/β-catenin signaling pathway in young growing rats (Sun et al, 2015). The bone mineral density and femoral ultrastructure have been decreased and damaged by AlCl 3 (Sun et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

“…Extracellular superoxide dismutase (SOD) manages the formation of hydrogen peroxide, whereas glutathione geroxidase (GSH-P x ) takes charge of the enzymatic catabolism of the ROS (Lubos et al, 2011). The activities of GSH-Px and SOD have been decreased, and the levels of ROS have been increased by AlCl 3 in bone (Sun et al, 2016a). Limited data showed the effects of Al on the GSH-P x , SOD and ROS in the osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

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The suppressive effects of aluminum chloride on the osteoblasts function

Zhu

Yan

et al. 2016

Environmental Toxicology and Pharmacology

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Aluminum (Al) exposure impairs bone formation, and bone formation is mediated by the osteoblasts. But effects of Al on the osteoblasts function remain elusive. The osteoblasts were exposed to 0, 0.0252, 0.126, 0.252mg/mL AlCl·6HO for 24h. The osteoblasts viability, TGF-β, BMP-2, IGF-I and Cbfα1 mRNA expressions, and GSH-P and SOD activities, ROS concentration were determined. The osteoblasts ultrastructural features were also observed. The results showed that AlCl suppressed the osteoblasts viability, TGF-β, BMP-2, IGF-I and Cbfα1 mRNA expressions, GSH-P and SOD activities, and elevated ROS concentration compared with the CG. The ultrastructural features of osteoblasts in the HG showed mitochondrial swelling, foam-like structure, uneven distribution of chromatin, incomplete cell membrane and cytoplasm spillover compared with the CG. It indicates that AlCl inhibits osteoblasts viability, growth regulation factors mRNA expressions, anti-oxidative function, and damaged the osteoblasts histology structure, impairing the osteoblasts function.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The suppressive effects of aluminum chloride on the osteoblasts function

Zhu

Yan

et al. 2016

Environmental Toxicology and Pharmacology

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“…The mechanism of TGF-β1 is as follows: the ligands combine with TGF-β receptors in cytomembrane, and type I receptors are activated; Type I receptors transmit signals to the intracellular media Smad-2/3; then those phosphorylated receptors of Smad-2/3 combine with Smad-4 and transduce TGF-β1 signals directly from the cytomembrane to the cell nucleus to control the expression of downstream target genes. Smad-2/3, the specific key factors in the TGF-β signal transduction pathway 33 , play a significant role in formation, remodeling, and maintenance of bone [34][35][36] . In this study, the expressions of TGF-β1, Smad-2/3 in group B were significantly increased compared with group A, suggesting that the mechanism of PMOP was related to the abnormal expression of transduction factors in the TGF-β1 and Smad signaling pathway.…”

Section: Effect On Bone Metabolism Markers and Tgf-β1/smad-2/3 Signalmentioning

confidence: 99%

Effects of Acupoint Application Therapy with TianGui Powder on Osteoporosis in Ovariectomized Rats through TGF‐β1 and Smad2/3 Signaling Pathway

Lin

Wang

Zhang

et al. 2019

Orthopaedic Surgery

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Objectives To explore the effects of acupoint application therapy (AAT) with TianGui Powder (TGP) on the expressions of the transforming growth factor β1 (TGF‐β1) and Smad‐2/3 signaling pathway in ovariectomized osteoporosis rats. Methods Sixty rats were randomly divided into four groups: normal group (group A), model group (group B), TGP group (group C), and Western medicine group (group D). Group A had only the corresponding amount of adipose tissue around the ovary removed; rats in the other groups had bilateral ovariectomies. After 1 week, groups A and B were given 1 mL/100 mg normal saline solution by gavage, group C was treated with AAT with TGP on ShenQue acupoint (0.2 piece/rat, 6 h/time, 1 time/d) and group D was given calcium carbonate vitamin D3 (36 mg/kg/d) and alfacalcidol (0.05 μg/kg/d) tablet suspension. In this study, the bone mineral density (BMD) , the levels of BALP, TRAP‐5b, and BGP in serum and the changes in bone histomorphology was detected. For acquiring lumbar experimental data, the expression of TGF‐β1, Smad‐2/3 proteins and mRNA of TGF‐β1and Smad‐2/3 were assessed. After 12 weeks, the data were collected for analysis. Results Compared with group A, the bone trabecula was thinner and significantly reduced in other groups. The result of BMD improved significantly in both groups C and D compared to group B after intervention ( P < 0.05). In contrast, compared to group B, the levels of BALP, TRAP‐5b, and BGP significantly declined in both groups C and D. In group C, the results of protein expressions in TGF‐β1, Smad‐2/3 were 2.870 ± 0.270, 1.552 ± 0.111, and 1.420 ± 0.079, respectively. In groups C and D, those indications significantly declined compared to group B ( P < 0.01). In group C, the level of mRNA expressions of TGF‐β1, Smad‐2/3 were 1.872 ± 0.177, 1.672 ± 0.086, and 1.790 ± 0.136, respectively. Compared with group B, those indications had significant difference in groups C and D ( P < 0.05). Conclusion Acupoint application therapy with TGP could significantly improve the BMD. The TGF‐β1 and Smad‐2/3 signaling pathway could be a therapeutic target of TGP in postmenopausal osteoporosis rats.

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“…Aluminum exposure impairs bone formation; inhibition of bone formation by aluminum through different signal transduction pathways has been reported [121]. Exposure to Al is associated with low bone mineral density (BMD) and an increased risk of osteoporosis [121][122][123][124]. Fluoride enhances the uptake of aluminum; the simultaneous administration of fluorine and aluminum increased plasma [125], and bone [126] concentrations of aluminum in rats, whereas aluminum suppresses the uptake of fluoride [127].…”

Section: Co-exposure With Other Elementmentioning

confidence: 99%

Progressive Research in the Molecular Mechanisms of Chronic Fluorosis

Shen¹,

Feng²,

Xia³

et al. 2019

Environmental Chemistry and Recent Pollution Control Approaches

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Long-term excessive intake of fluoride (F) leads to chronic fluorosis, resulting in dental fluorosis and skeletal fluorosis. Chronic exposure to high doses of fluoride can also cause damage to soft tissues, especially when it passes through the blood-brain, blood-testis, and blood-placenta barrier, causing damage to the corresponding tissues. Fluorosis has become a public health problem in some countries or regions around the world. Understanding the pathogenesis of fluorosis is very important. Although the exact mechanism of fluorosis has not been fully elucidated, various mechanisms of fluoride-induced toxicity have been proposed. In this chapter, we will introduce the research progress of the mechanism of fluorosis, focusing on dental fluorosis, skeletal fluorosis, nervous and reproductive system toxicity, and influential factors related to fluoride toxicity (i.e., genetic background, co-exposure with other element). In addition, the application of proteomics and metabolomics in the study of the pathogenesis of fluorosis is also introduced. Currently, there is still no specific treatment for fluorosis. However, since fluorosis is caused by excessive intake of fluoride, avoiding excessive fluoride intake is the critical measure to prevent the disease. In endemic regions, health education and supplement diet with vitamins C, D and E, and calcium and antioxidant compounds are important.

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Aluminum trichloride induces bone impairment through TGF-β1/Smad signaling pathway

Cited by 25 publications

References 45 publications

The suppressive effects of aluminum chloride on the osteoblasts function

The suppressive effects of aluminum chloride on the osteoblasts function

Effects of Acupoint Application Therapy with TianGui Powder on Osteoporosis in Ovariectomized Rats through TGF‐β1 and Smad2/3 Signaling Pathway

Progressive Research in the Molecular Mechanisms of Chronic Fluorosis

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