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Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats

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Abstract

This study evaluated the effects of metformin on orthodontic tooth movement in a rat model of type 2 diabetes mellitus. Rats were fed a high-fat diet for 4 weeks to induce fat accumulation and insulin resistance, and then injected with a low dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetes. An orthodontic appliance was placed in normoglycemic, type 2 diabetes, and type 2 diabetes with metformin-administrated rats. After 14 days, type 2 diabetes rats exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphatase-positive osteoclasts, stronger cathepsin K expression, and weaker alkaline phosphatase immunostaining than normoglycemic rats. Metformin administration resulted in normalization of osteoclast numbers, cathepsin K immunostaining, and of tooth movement as well as partly recovery of alkaline phosphatase expression in diabetic rats. Metformin also reduced sclerostin expression and improved the immunolocalization of dentin matrix protein 1 in osteocytes of type 2 diabetes rats. These results suggest that metformin administration reversed the adverse effects of diabetes on orthodontic tooth movement.

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Acknowledgements

This study was partially supported by the National Nature Science Foundation of China (Nos. 81271965; 81470719; 8151101150) to Li M. The Shandong Province Science and Technique Foundation, China (No. 2014GSF118093) to Guo J.

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Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Bone Metabolism, School of Stomatology, Shandong University, Wenhua West Road 44-1, Jinan, 250012, China

    Jing Sun, Juan Du, Wei Feng, Hongrui Liu, Jie Guo & Minqi Li

  2. West China School of Stomatology, Sichuan University, Chengdu, China

    Boyao Lu

  3. Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan

    Norio Amizuka

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  1. Jing Sun
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  2. Juan Du
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  3. Wei Feng
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  4. Boyao Lu
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  5. Hongrui Liu
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Correspondence to Minqi Li.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Sun, J., Du, J., Feng, W. et al. Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats. J Mol Hist 48, 73–81 (2017). https://doi.org/10.1007/s10735-016-9707-y

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