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Role of TGF-β1 in Fluoride-Treated Osteoblasts at Different Stages

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Abstract

Little attention has been paid to the tolerance of osteoblasts to fluoride in distinct differentiation stages, and the role of TGF-β1 in fluoride-treated osteoblast differentiation of progenitors and precursors was rarely mentioned in previous studies. The present study aimed to clarify how fluoride affected different differentiation stages of osteoblasts, and to elucidate the role of TGF-β1 in this process. We assessed cell migration, proliferation, DNA damage, and apoptosis of early-differentiated osteoblasts derived from bone marrow stem cells (BMSCs) exposed to fluoride with or without TGF-β1. Subsequently, MC3T3-E1 cells cultured with mineral induction medium were treated with fluoride to test fluoride’s effect on late-differentiated osteoblasts. The specific fluoride concentrations and treatment times were chosen to evaluate the role of TGF-β1 in fluoride-induced osteoblastic differentiation and function. Results showed early-differentiated osteoblasts treated with a low dose of fluoride grew and moved more rapidly. TGF-β1 promoted cell proliferation and inhibited cell apoptosis in early-differentiated osteoblasts exposed to a low fluoride dose, but enhanced apoptosis at higher fluoride conditions. In the late-differentiated osteoblasts, the fluorine dose range with anabolic effects was narrowed, and the fluoride range with catabolic effects was widened. Treatment with a low fluoride dose stimulated the alkaline phosphatase (ALP) expression. TGF-β1 treatment inhibited Runx2 expression but increased RANKL expression in late-differentiated osteoblasts exposed to fluoride. Meanwhile, TGF-β1 treatments activated Smad3 phosphorylation but blocked Wnt10b expression in osteoblasts. We conclude that TGF-β1 plays an essential role in fluoride-induced differentiation and osteoblast function via activation of Smad3 instead of Wnt10 signaling.

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Funding

This work was supported by grants from the Natural Science Foundation of Jilin Province of China (20180101151JC) and the National Natural Science Foundation of China [81673111].

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Authors and Affiliations

  1. Department of Regenerative Medical Science, School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, People’s Republic of China

    Ningning Jiang, Wenshu Xu, Zhongyuan Zhang, Yang Yang, Jingmin Zhang & Hui Xu

  2. China-Japan Union Hospital, Jilin University, Changchun, 130033, People’s Republic of China

    Hui Jin

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  1. Ningning Jiang
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Jiang, N., Xu, W., Zhang, Z. et al. Role of TGF-β1 in Fluoride-Treated Osteoblasts at Different Stages. Biol Trace Elem Res 200, 740–748 (2022). https://doi.org/10.1007/s12011-021-02686-2

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