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

Author:

Wan Yu1,Mo Li-jun1,Wu Lu2,Li Dong-li1,Song Jia1,Hu You-kun1,Huang Hai-bin1,Wei Qin-zhi1,Wang Da-peng3,Qiu Jian-min4,Zhang Zi-ji5,Liu Qi-zhan2,Yang Xing-fen1

Affiliation:

1. Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, Guangdong-Hongkong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Public Health, Southern Medical University , Guangzhou, Guangdong 510515, People’s Republic of China

2. Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University , Nanjing, Jiangsu 211166, People’s Republic of China

3. The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University , Guiyang, Guizhou 550025, People’s Republic of China

4. Department of Ultrasound Medicine, The Fifth Affiliated Hospital of Southern Medical University , Guangzhou, Guangdong 510920, People’s Republic of China

5. Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong 510080, People’s Republic of China

Abstract

AbstractCadmium (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 (CdCl2) 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 CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.

Funder

National Natural Science Foundation of China

Guangdong Science and Technology Department

Key Laboratory of Environmental Pollution Monitoring and Disease Control

Ministry of Education

Guizhou Medical University

Publisher

Oxford University Press (OUP)

Subject

Toxicology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3