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Geraniol attenuates osteoclast differentiation by suppressingNF-kB activity and expression of osteoclastogenic genes

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Abstract

Osteoporotic patients have lower bone mass due to increased bone resorption by osteoclasts. The aim of this study was to investigate the cytotoxic and anti-osteoclastogenic effects of geraniol, a natural monoterpene on human CD14+ monocytes (ex vivo) and murine RAW264.7 macrophages (in vitro) using alamar blue and tartrate resistant acid phosphatase staining respectively. The anti-osteoclastogenic activity of geraniol was further explored by analyzing its effects on actin ring formation and bone resorptive function of osteoclasts. Geraniol significantly (p < 0.001) inhibited osteoclast formation in CD14+ monocytes and RAW264.7 macrophages without cytotoxicity. Moreover, reduced osteoclastogenesis in these cells led to an arrest in actin ring formation and diminished bone resorption. Analysis of underlying molecular mechanisms revealed that geraniol alleviated NF-kB activity, an indispensable upstream modulator of osteoclast formation. Furthermore, expression of key osteoclastogenic genes such as dendritic cell-specific transmembrane protein (DC-STAMP) involved in cell-cell fusion and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor essential for osteoclast differentiation was downregulated by geraniol. These observations indicate that inhibition of osteoclast differentiation is presumably one of the pharmacological properties of geraniol.

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Acknowledgments

This study was supported by grants from the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship; RESCOM, University of Pretoria and the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition, and Well-being.

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Authors and Affiliations

  1. Department of Physiology, University of Pretoria, Pretoria, South Africa

    Vishwa Deepak & Magdalena Coetzee

  2. School of Food and Nutrition, Massey Institute of Food Science and Technology, Massey University, Palmerston North, New Zealand

    Marlena C Kruger

  3. Department of Human Nutrition, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Marlena C Kruger

  4. Associate of the Institute for Food, Nutrition and Well-being, University of Pretoria, Pretoria, South Africa

    Marlena C Kruger & Magdalena Coetzee

Authors
  1. Vishwa Deepak
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  2. Marlena C Kruger
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  3. Magdalena Coetzee
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Correspondence to Magdalena Coetzee.

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The authors declare that they have no competing interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Human Research Ethics Committee of the Faculty of Health Sciences, University of Pretoria (Protocol approval number: 67/2014) and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.

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Deepak, V., Kruger, M.C. & Coetzee, M. Geraniol attenuates osteoclast differentiation by suppressingNF-kB activity and expression of osteoclastogenic genes. Med Chem Res 26, 19–26 (2017). https://doi.org/10.1007/s00044-016-1715-7

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  • DOI: https://doi.org/10.1007/s00044-016-1715-7

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