2. Academic Validation
  3. Bone morphogenetic protein 4 is involved in cadmium-associated bone damage

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

  • Toxicol Sci. 2022 Dec 1;kfac121. doi: 10.1093/toxsci/kfac121.
Yu Wan 1,  Li-Jun Mo 1,  Lu Wu 2,  Dong-Li Li 1,  Jia Song 1,  You-Kun Hu 1,  Hai-Bin Huang 1,  Qin-Zhi Wei 1,  Da-Peng Wang 3,  Jian-Ming Qiu 4,  Zi-Ji Zhang 5,  Qi-Zhan Liu 2,  Xing-Fen Yang 1
Affiliations

Affiliations

  • 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, 510515, Guangdong, 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, 211166, Jiangsu, People's Republic of China.
  • 3 The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550025, Guizhou, People's Republic of China.
  • 4 Department of Ultrasound Medicine, The Fifth Affiliated Hospital of Southern Medical University, 566 Congcheng Avenue, Conghua District Guangzhou.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People's Republic of China.
PMID: 36453845 DOI: 10.1093/toxsci/kfac121
Abstract

Cadmium is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. BMP/SMAD signaling pathway can mediate osteogenic differentiation, but the association between cadmium 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 were treated with 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 cadmium-associated bone damage. Our results show 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%CI 7.47, 85.00) of the total association between the cadmium and the risk of cadmium-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared to CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for cadmium-associated bone damage.

Keywords

BMP; SMAD; bone damage; cadmium; osteogenic differentiation.

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