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Article Open Access

Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice

  • Authors:
    • Xue-Ju Li
    • Zhe Zhu
    • Si-Lin Han
    • Zi-Long Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1661-1672
    |
    Published online on: November 2, 2016
       https://doi.org/10.3892/ijmm.2016.2794
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Abstract

Diabetes, as a serious metobolic disorder, poses global threat to human health. It is estimated that over 50 million individuals are already affected by diabetes. Currently, diabetes-related osteoporosis has been a research hotspot due to its high incidence rate in older individuals. Osteoprotegerin, as an important protein for the prevention of osteoporosis, has been proven to be key to the suppression of osteoporosis. Hence, the loss of function of osteoprotegerin may promote the development of osteoporosis. Bergapten, as a natural anti-inflammatory and anti-tumor agent isolated from bergamot essential oil, other citrus essential oils, and grapefruit juice, has been proven to have the ability to attenuate a number of metabolic disorders. In view of these findings, in this study, we used a high-fat diet to construct a mouse model of diabetes-related osteoporosis and a mouse model of diabetes-related osteoporosis using osteoprotegerin knockout mice. Enzyme-linked immunosorbent assay (ELISA), qPCR, western blot analysis, immunohistochemical assay, H&E staining, Oil Red O staining, Masson's staining and other biochemical analyses were used to evaluate the related signaling pathways involved in the development of diabetes-related osteoporosis. We also examined the role of osteoprotegerin in the activation of these pathways and in the development of osteoporosis, as well as the protective effects of bergapten against diabetes-related osteoporosis and on the activation of related signaling pathways. Our results revealed that in diabetes-related osteoporosis, the phosphoinositide 3-kinase (PI3K)/AKT, c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways were activated and the expression levels of related indicators were increased. At the same time, osteoprotegerin knockout further promoted the activation of these pathways. By contrast, bergapten exerted effects similar to those of osteoprotegerin. Bergapten exhibited the ability to significantly inhibit RANKL-RANK signaling transduction, and to suppress the activation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways, thus protecting trabecular structure and decreasing osteoclastogenic differentiation.
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Copy and paste a formatted citation
Spandidos Publications style
Li X, Zhu Z, Han S and Zhang Z: Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice. Int J Mol Med 38: 1661-1672, 2016.
APA
Li, X., Zhu, Z., Han, S., & Zhang, Z. (2016). Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice. International Journal of Molecular Medicine, 38, 1661-1672. https://doi.org/10.3892/ijmm.2016.2794
MLA
Li, X., Zhu, Z., Han, S., Zhang, Z."Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice". International Journal of Molecular Medicine 38.6 (2016): 1661-1672.
Chicago
Li, X., Zhu, Z., Han, S., Zhang, Z."Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice". International Journal of Molecular Medicine 38, no. 6 (2016): 1661-1672. https://doi.org/10.3892/ijmm.2016.2794
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, Zhu Z, Han S and Zhang Z: Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice. Int J Mol Med 38: 1661-1672, 2016.
APA
Li, X., Zhu, Z., Han, S., & Zhang, Z. (2016). Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice. International Journal of Molecular Medicine, 38, 1661-1672. https://doi.org/10.3892/ijmm.2016.2794
MLA
Li, X., Zhu, Z., Han, S., Zhang, Z."Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice". International Journal of Molecular Medicine 38.6 (2016): 1661-1672.
Chicago
Li, X., Zhu, Z., Han, S., Zhang, Z."Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-κB signaling pathways in osteoprotegerin knockout mice". International Journal of Molecular Medicine 38, no. 6 (2016): 1661-1672. https://doi.org/10.3892/ijmm.2016.2794
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