Chronic intake of fluoride, existing in the environment, may cause endemic fluorosis, which is characterized by the occurrence of skeletal and dental fluorosis. However, the pathogenesis of fluorosis has not yet been elucidated. Abnormal osteoblast proliferation and activation have a pivotal role in bone turnover disorders which are linked to skeletal fluorosis. MicroRNAs are involved in fundamental cellular processes, including cell proliferation. Based on our previous study, population study and in vitro experiments were designed to understand the effect of miR-122-5p on osteoblast activation in skeletal fluorosis through targeting cyclin-dependent kinase 4 (CDK4). In human populations with coal-burning type fluoride exposure, the results showed that miR-122-5p was downregulated but CDK4 expression was upregulated and miR-122-5p was negatively correlated with CDK4 expression. Furthermore, in human osteoblasts treated with sodium fluoride, we demonstrated that miR-122-5p mediated osteoblast activation of skeletal fluorosis via upregulation of the CDK4 protein. In support of this, dual-luciferase reporter assay showed that miR-122-5p modulated CDK4 protein levels by targeting its 3′-untranslated region. These findings show, for the first time, that miR-122-5p may be involved in the cause and development of skeletal fluorosis by targeting CDK4.

长期摄入环境中的氟化物可能会导致地方性氟中毒，其特征是骨骼和牙齿氟中毒的发生。但是，氟中毒的发病机理尚未阐明。异常的成骨细胞增殖和活化在与骨骼氟中毒有关的骨转换障碍中起关键作用。MicroRNA参与基本的细胞过程，包括细胞增殖。在之前的研究基础上，设计了人群研究和体外实验，以了解miR-122-5p通过靶向细胞周期蛋白依赖性激酶4（CDK4）对骨骼氟症中成骨细胞活化的影响）。在有燃煤型氟化物暴露的人群中，结果显示miR-122-5p被下调，而CDK4表达被上调，而miR-122-5p与CDK4表达负相关。此外，在用氟化钠处理的人成骨细胞中，我们证明了miR-122-5p通过上调CDK4蛋白介导了骨骼氟中毒的成骨细胞活化。支持这一点的是，双重荧光素酶报告基因测定表明，miR-122-5p通过靶向其3'-非翻译区来调节CDK4蛋白的水平。这些发现首次表明，miR-122-5p可能通过靶向CDK4参与氟中毒的发生和发展。