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Bone morphogenetic protein 4 is involved in cadmium-associated bone damage

Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illum...

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Autores principales: Wan, Yu, Mo, Li-jun, Wu, Lu, Li, Dong-li, Song, Jia, Hu, You-kun, Huang, Hai-bin, Wei, Qin-zhi, Wang, Da-peng, Qiu, Jian-min, Zhang, Zi-ji, Liu, Qi-zhan, Yang, Xing-fen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936213/
https://www.ncbi.nlm.nih.gov/pubmed/36453845
http://dx.doi.org/10.1093/toxsci/kfac121
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author Wan, Yu
Mo, Li-jun
Wu, Lu
Li, Dong-li
Song, Jia
Hu, You-kun
Huang, Hai-bin
Wei, Qin-zhi
Wang, Da-peng
Qiu, Jian-min
Zhang, Zi-ji
Liu, Qi-zhan
Yang, Xing-fen
author_facet Wan, Yu
Mo, Li-jun
Wu, Lu
Li, Dong-li
Song, Jia
Hu, You-kun
Huang, Hai-bin
Wei, Qin-zhi
Wang, Da-peng
Qiu, Jian-min
Zhang, Zi-ji
Liu, Qi-zhan
Yang, Xing-fen
author_sort Wan, Yu
collection PubMed
description Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl(2)) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl(2) only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.
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spelling pubmed-99362132023-02-18 Bone morphogenetic protein 4 is involved in cadmium-associated bone damage Wan, Yu Mo, Li-jun Wu, Lu Li, Dong-li Song, Jia Hu, You-kun Huang, Hai-bin Wei, Qin-zhi Wang, Da-peng Qiu, Jian-min Zhang, Zi-ji Liu, Qi-zhan Yang, Xing-fen Toxicol Sci Biomarkers Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl(2)) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl(2) only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage. Oxford University Press 2022-12-01 /pmc/articles/PMC9936213/ /pubmed/36453845 http://dx.doi.org/10.1093/toxsci/kfac121 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Biomarkers
Wan, Yu
Mo, Li-jun
Wu, Lu
Li, Dong-li
Song, Jia
Hu, You-kun
Huang, Hai-bin
Wei, Qin-zhi
Wang, Da-peng
Qiu, Jian-min
Zhang, Zi-ji
Liu, Qi-zhan
Yang, Xing-fen
Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title_full Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title_fullStr Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title_full_unstemmed Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title_short Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
title_sort bone morphogenetic protein 4 is involved in cadmium-associated bone damage
topic Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936213/
https://www.ncbi.nlm.nih.gov/pubmed/36453845
http://dx.doi.org/10.1093/toxsci/kfac121
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