Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, 641046, India.
Arch Toxicol. 2024 Dec;98(12):3913-3932. doi: 10.1007/s00204-024-03853-9. Epub 2024 Sep 13.
Fluoride-induced toxicity (fluorosis) poses a significant health concern globally, affecting millions of individuals. Understanding the molecular mechanisms underlying fluorosis, particularly the role of microRNAs (miRNAs), is crucial for developing effective preventive and therapeutic strategies. This review explores the pivotal role of miRNAs in the pathogenesis of fluorosis, particularly examining its impact on both hard (skeletal and dental) and soft (brain, liver, kidney, heart, and reproductive organs) tissues. Skeletal fluorosis manifests as abnormal bone mineralization and structure, while dental fluorosis affects enamel formation. In vitro and in vivo studies suggest a significant involvement of miRNAs in the progression of these conditions. For skeletal fluorosis, miR-124, miR-155, and miR-200c-3p have been identified as key regulators, while miR-296-5p and miR-214-3p are implicated in dental fluorosis. Moreover, soft tissue fluorosis encompasses a spectrum of adverse effects on various organs, including the brain, liver, kidneys, heart, and reproductive system. In soft tissues, miRNAs, such as miR-124, miR-200c-3p, miR-132, and miR-34b-5p, have been linked to cellular damage and dysfunction. Notably, miRNAs exert their effects through the modulation of critical pathways involved in fluorosis pathology, including Wnt signaling, apoptosis, cell cycle, and autophagy. Understanding the regulatory roles of miRNAs in fluorosis pathogenesis holds promise for identifying biomarkers and therapeutic targets. However, further research is needed to elucidate the molecular mechanisms underlying miRNA-mediated responses to fluoride exposure. Integration of miRNA research into fluorosis studies could facilitate the development of diagnostic tools and therapeutic interventions, thus mitigating the detrimental effects of fluorosis on both hard and soft tissues.
氟诱导毒性（氟中毒）是一个全球性的重大健康问题，影响着数以百万计的人。了解氟中毒的分子机制，特别是 microRNAs（miRNAs）的作用，对于开发有效的预防和治疗策略至关重要。本综述探讨了 miRNAs 在氟中毒发病机制中的关键作用，特别研究了其对硬组织（骨骼和牙齿）和软组织（脑、肝、肾、心脏和生殖器官）的影响。骨骼氟中毒表现为骨矿物质化和结构异常，而牙齿氟中毒影响釉质形成。体外和体内研究表明，miRNAs 显著参与了这些疾病的进展。对于骨骼氟中毒，miR-124、miR-155 和 miR-200c-3p 被确定为关键调节剂，而 miR-296-5p 和 miR-214-3p 则与牙齿氟中毒有关。此外，软组织氟中毒包括对各种器官（包括脑、肝、肾、心脏和生殖系统）的一系列不利影响。在软组织中，miRNAs，如 miR-124、miR-200c-3p、miR-132 和 miR-34b-5p，与细胞损伤和功能障碍有关。值得注意的是，miRNAs 通过调节参与氟中毒病理的关键途径发挥作用，包括 Wnt 信号通路、细胞凋亡、细胞周期和自噬。了解 miRNAs 在氟中毒发病机制中的调节作用有望为鉴定生物标志物和治疗靶点提供线索。然而，需要进一步的研究来阐明 miRNA 介导的对氟暴露反应的分子机制。将 miRNA 研究纳入氟中毒研究中，可以促进诊断工具和治疗干预措施的发展，从而减轻氟中毒对硬组织和软组织的不利影响。
