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miR-122-5p Mediates Fluoride-Induced Osteoblast Activation by Targeting CDK4

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Abstract

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.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81660524) and the First-Class Discipline Construction Project in Guizhou Province - Public Health and Preventive Medicine (No. 2017[85]).

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Authors and Affiliations

  1. School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China

    Chen Li, Ting Ouyang, Maolin Yao, Aihua Zhang, Peng Luo & Xueli Pan

  2. Guizhou Orthopedics Hospital, Guiyang, 550007, China

    Yu Qin

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  1. Chen Li
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Correspondence to Xueli Pan.

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Highlights

• miR-122-5p levels were downregulated, and CDK4 expression was upregulated in the fluoride-exposed population.

• Downregulation of miR-122-5p is involved in fluoride-induced human osteoblast activation by increasing the CDK4 protein expression.

• miR-122-5p regulates CDK4 protein expression by targeting its 3′-UTR.

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Li, C., Qin, Y., Ouyang, T. et al. miR-122-5p Mediates Fluoride-Induced Osteoblast Activation by Targeting CDK4. Biol Trace Elem Res 199, 1215–1227 (2021). https://doi.org/10.1007/s12011-020-02239-z

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