Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway

Ying Lv; Jin Yao; Yang Wang; Guohui Bai; Changhu Lin; Chenglong Tu

doi:10.1016/j.envres.2024.118527

Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway

Environ Res. 2024 Feb 21:250:118527. doi: 10.1016/j.envres.2024.118527. Online ahead of print.

Authors

Ying Lv¹, Jin Yao¹, Yang Wang², Guohui Bai³, Changhu Lin⁴, Chenglong Tu⁵

Affiliations

¹ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed By the Province and Ministry, Guizhou Medical University, Guiyang, 550025, China.
² Infrastructure Construction Department, Guizhou Medical University, Guiyang, 550025, China.
³ Key Laboratory of Oral Disease Research, School of Stomatology, Zunyi Medical University, Zunyi, China.
⁴ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed By the Province and Ministry, Guizhou Medical University, Guiyang, 550025, China. Electronic address: linchanghu79@sina.com.
⁵ Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, China; Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed By the Province and Ministry, Guizhou Medical University, Guiyang, 550025, China. Electronic address: chenglongtu@163.com.

PMID: 38387489
DOI: 10.1016/j.envres.2024.118527

Abstract

Fluoride (F) and sulfur dioxide (SO₂) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO₂ can cause abnormal enamel mineralization. Ameloblastin (AMBN) plays a crucial role in the process of enamel mineralization. However, the process by which simultaneous exposure to F and SO₂ influences enamel formation by regulating AMBN expression still needs to be understood. This study aimed to establish in vivo and in vitro models of F-SO₂ Co-exposure and investigate the relationship between AMBN and abnormal enamel mineralization. By overexpressing/knocking out the Fibroblast Growth Factor 9 (FGF9) gene, we investigated the impact of FGF9-mediated Mitogen-Activated Protein Kinase (MAPK) signaling on AMBN synthesis to elucidate the mechanism underlying the induction of abnormal enamel mineralization by F-SO₂ Co-exposure in rats. The results showed that F-SO₂ exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO₂, gradual increases in the protein expression of FGF9 and phosphorylated p38 mitogen-activated protein kinase (p-P38) were observed. Conversely, the protein levels of AMBN, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated c-Jun N-terminal kinase (p-JNK) were decreased. AMBN expression was significantly correlated with FGF9, p-ERK, and p-JNK expression in ameloblasts. Interestingly, FGF9 overexpression reduced the levels of p-ERK and p-JNK, worsening the inhibitory effect of F-SO₂ on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO₂-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO₂-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways.

Keywords: Enamel; FGF9; Fluoride; MAPK; Mineralization; SO(2).