Fluoride resistance capacity in mammalian cells involves global gene expression changes associate with ferroptosis

Yi Zhang; Yimin Fang; Shen Zhao; Jialong Wu; Chenkang Lu; Lai Jiang; Shujun Ran; Jia Wang; Fei Sun; Bin Liu

doi:10.1016/j.cbi.2023.110555

Fluoride resistance capacity in mammalian cells involves global gene expression changes associate with ferroptosis

Chem Biol Interact. 2023 Aug 25:381:110555. doi: 10.1016/j.cbi.2023.110555. Epub 2023 May 26.

Authors

Yi Zhang¹, Yimin Fang², Shen Zhao¹, Jialong Wu¹, Chenkang Lu¹, Lai Jiang¹, Shujun Ran¹, Jia Wang¹, Fei Sun¹, Bin Liu³

Affiliations

¹ Department of Endodontics and Operative Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
² Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
³ Department of Endodontics and Operative Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China. Electronic address: pizzanet@163.com.

PMID: 37245782
DOI: 10.1016/j.cbi.2023.110555

Abstract

Objective: The purpose of this study was to understand mouse osteoblast ferroptosis under high fluoride environment by stimulating fluoride levels to corresponding levels. In order to define the underlying mechanism of fluoride resistance in mammals and provide a theoretical basis for fluorosis treatment, high-throughput sequencing was applied to map the genetic changes of fluoride-resistant mouse osteoblasts and analyze the role of ferroptosis-related genes.

Methods: Cell Counting Kit-8, Reactive Oxygen Species Assay Kit and C11 BODIPY 581/591 were used to monitor proliferation and ferroptosis of mouse osteoblasts MC3T3-E1 under high fluoride environment. Fluoride-tolerant MC3T3-E1 cells were developed by gradient fluoride exposure. The differentially expressed genes of fluorine-resistant MC3T3-E1 cells were identified by high-throughput sequencing.

Results: MC3T3-E1 cells cultured in medium containing 20, 30, 60, 90 ppm F^- exhibited decreased viability and increased reactive oxygen species and lipid peroxidation levels in correlation with F^- concentrations. High-throughput RNA sequencing identified 2702 differentially expressed genes (DEGs) showed more than 2-fold difference in 30 ppm FR MC3T3-E1 cells, of which 17 DEGs were associated with ferroptosis.

Conclusion: High fluoride environment affected the content of lipid peroxides in the body and increased the level of ferroptosis, further, ferroptosis-related genes played specific roles in the fluoride resistance of mouse osteoblasts.

Keywords: Ferroptosis; Fluoride resistance; Fluorosis; Skeletal fluorosis.

MeSH terms

Animals
Cell Differentiation / genetics
Cell Line
Ferroptosis*
Fluorides* / metabolism
Fluorides* / toxicity
Gene Expression
Mammals / metabolism
Mice
Osteoblasts / metabolism
Reactive Oxygen Species / metabolism

Substances

Fluorides
Reactive Oxygen Species