PMID- 38387489 OWN - NLM STAT- Publisher LR - 20240302 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 250 DP - 2024 Feb 21 TI - Co-exposure to fluoride and sulfur dioxide induces abnormal enamel mineralization in rats via the FGF9-mediated MAPK signaling pathway. PG - 118527 LID - S0013-9351(24)00431-6 [pii] LID - 10.1016/j.envres.2024.118527 [doi] AB - Fluoride (F) and sulfur dioxide (SO(2)) contamination is recognized as a public health concern worldwide. Our previous research has shown that Co-exposure to F and SO(2) 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 SO(2) 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-SO(2) 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-SO(2) Co-exposure in rats. The results showed that F-SO(2) exposure damaged the structure of rat enamel and ameloblasts. When exposed to F or SO(2), 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-SO(2) on AMBN. Conversely, FGF9 knockout increased the phosphorylation of ERK and JNK, partially reversing the F-SO(2)-induced downregulation of AMBN. Taken together, these findings strongly demonstrate that FGF9 plays a critical role in F-SO(2)-induced abnormal enamel mineralization by regulating AMBN synthesis through the JNK and ERK pathways. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Lv, Ying AU - Lv Y AD - 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. FAU - Yao, Jin AU - Yao J AD - 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. FAU - Wang, Yang AU - Wang Y AD - Infrastructure Construction Department, Guizhou Medical University, Guiyang, 550025, China. FAU - Bai, Guohui AU - Bai G AD - Key Laboratory of Oral Disease Research, School of Stomatology, Zunyi Medical University, Zunyi, China. FAU - Lin, Changhu AU - Lin C AD - 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. FAU - Tu, Chenglong AU - Tu C AD - 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. LA - eng PT - Journal Article DEP - 20240221 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 SB - IM OTO - NOTNLM OT - Enamel OT - FGF9 OT - Fluoride OT - MAPK OT - Mineralization OT - SO(2) COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/23 00:42 MHDA- 2024/02/23 00:42 CRDT- 2024/02/22 19:12 PHST- 2023/12/19 00:00 [received] PHST- 2024/01/25 00:00 [revised] PHST- 2024/02/19 00:00 [accepted] PHST- 2024/02/23 00:42 [pubmed] PHST- 2024/02/23 00:42 [medline] PHST- 2024/02/22 19:12 [entrez] AID - S0013-9351(24)00431-6 [pii] AID - 10.1016/j.envres.2024.118527 [doi] PST - aheadofprint SO - Environ Res. 2024 Feb 21;250:118527. doi: 10.1016/j.envres.2024.118527.