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Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride

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Abstract

The role of insulin in the mechanism underlying the excessive fluoride that causes skeletal lesion was studied. The in vitro bone marrow stem cells (BMSC) collected from Kunming mice were exposed to varying concentrations of fluoride with or without insulin. The cell viability and early differentiation of BMSC co-treated with fluoride and insulin were measured by using cell counting kit-8 and Gomori modified calcium–cobalt method, respectively. We further investigated the in vivo effects of varying dose of fluoride on rats co-treated with streptozotocin (STZ). Wistar rats were divided into six groups which included normal control, 10 mg fluoride/kg day group, 20 mg fluoride/kg day group, STZ control, STZ + 10 mg fluoride/kg day group, and STZ + 20 mg fluoride/kg day group. The rats were administered with sodium fluoride (NaF) by gavage with water at doses 10 and 20 mg fluoride/kg day for 2 months. In a period of one month, half of rats in every group were treated with streptozotocin (STZ) once through intraperitoneal injection at 52 mg/kg body weight. The serum glucose, HbA1c, and insulin were determined. Bone mineral content and insulin release were assessed. The results showed insulin combined with fluoride stimulated BMSC cell viability in vitro. The bone mineral content reduced in rats treated with higher dose of fluoride and decreased immensely in rat co-treated with fluoride and STZ. Similarly, a combination treatment of a high dose of fluoride and STZ decreased insulin sensitivity and activity. To sum up, these data indicated fluoride influenced insulin release, activity, and sensitivity. Furthermore, the insulin state in vivo interfered in the osteogenesis in turn and implied there was a close relation between insulin and bone pathogenesis in the mechanism of fluoride toxicity.

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Acknowledgments

This work was supported by grants for skeletal fluorosis research from the National Natural Science Foundation of China (81072249), the Norman Bethune Program of Jilin University (2012222), and Specialized Research Fund for the Doctoral Program of Higher Education (20130061110084).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People’s Republic of China

    Chen Yang, Yan Wang & Hui Xu

  2. Center of Osteoporosis, the Forth Clinical Hospital, Jilin University, Changchun, 130041, China

    Mengmeng Zhang, Yagang Li, Weixian Mao & Yuan Gao

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  1. Chen Yang
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  2. Mengmeng Zhang
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  3. Yagang Li
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  4. Yan Wang
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  5. Weixian Mao
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  6. Yuan Gao
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  7. Hui Xu
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Correspondence to Hui Xu.

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Yang, C., Zhang, M., Li, Y. et al. Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride. Biol Trace Elem Res 168, 453–461 (2015). https://doi.org/10.1007/s12011-015-0374-8

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  • DOI: https://doi.org/10.1007/s12011-015-0374-8

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