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Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor

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Abstract

It is now widely recognized that purinergic signaling plays an important role in the regulation of bone remodeling. One receptor subtype, which has been suggested to be involved in this regulation, is the P2Y2 receptor (P2Y2R). In the present study, we investigated the effect of P2Y2R overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both mineral apposition rate and thickness of the endocortical osteoid layer were higher in the P2Y2R-Tg rats. μCT analysis showed reduced trabecular thickness and structural model index in P2Y2R-Tg rats. Femoral length was increased in the P2Y2R-Tg rats compared to Wt rats. In vitro, there was an increased formation of osteoclasts, but no change in total resorption in cultures from P2Y2R-Tg rats. The formation of mineralized nodules was significantly reduced in the osteoblastic cultures from P2Y2R-Tg rats. In conclusion, our study suggests that P2Y2R is involved in regulation of bone turnover, due to the effects on both osteoblasts and osteoclasts and that these effects might be relevant in the regulation of bone growth.

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Acknowledgements

This work was partially supported by the start-up funds from University of Missouri, National Institute of Health (grant no. P40 OD011062) and by the European Commission under the 7th Framework Programme (proposal no. 202231) performed as a collaborative project among the members of the ATPBone Consortium (Copenhagen University, University College London, University of Maastricht, University of Ferrara, University of Liverpool, University of Sheffield, and Université Libre de Bruxelles), and is a substudy under the main study “Fighting osteoporosis by blocking nucleotides: purinergic signalling in bone formation and homeostasis.”

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    Maria Ellegaard, Solveig Petersen, Ankita Agrawal, Lars Schack Kruse & Niklas Rye Jørgensen

  2. College of Veterinary Medicine, University of Missouri, Columbia, MO, USA

    Cansu Agca & Yuksel Agca

  3. Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

    Ankita Agrawal, Ning Wang & Alison Gartland

  4. Osteoporosis and Bone Metabolic Unit, Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

    Jens-Erik Beck Jensen

  5. OPEN, Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark

    Niklas Rye Jørgensen

Authors
  1. Maria Ellegaard
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  2. Cansu Agca
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  3. Solveig Petersen
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  4. Ankita Agrawal
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  5. Lars Schack Kruse
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  6. Ning Wang
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  7. Alison Gartland
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  8. Jens-Erik Beck Jensen
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  9. Niklas Rye Jørgensen
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  10. Yuksel Agca
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Contributions

Concept and design of the study: YA, NRJ, CA, AG. Conducting experiments: CA, YA, LSK, NW. Acquiring data: CA, YA, NRJ, SP, ME, AA, LSK, NW, AG, JEBJ. Analyzing data: NRJ, YA, CA, ME, SP, LSK, NW, AA, AG. Providing reagents and animal model: YA, CA. Writing, critically reviewing and approving the manuscript: NRJ, YA, CA, ME, SP, LSK, NW, AA, AG, JEBJ.

Corresponding authors

Correspondence to Niklas Rye Jørgensen or Yuksel Agca.

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Ethical approval

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 at which the studies were conducted.

Conflict of interest

Maria Ellegaard declares that she has no conflict of interest.

Cansu Agca declares that she has no conflict of interest.

Solveig Petersen declares that she has no conflict of interest.

Ankita Agrawal declares that she has no conflict of interest.

Lars Schack Kruse declares that he has no conflict of interest.

Ning Wang declares that he/she has no conflict of interest.

Alison Gartland declares that she has no conflict of interest.

Jens-Erik Beck Jensen declares that he has no conflict of interest.

Niklas Rye Jørgensen declares that he has no conflict of interest.

Yuksel Agca declares that he has no conflict of interest.

Additional information

Maria Ellegaard and Cansu Agca are joint-first authors.

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Ellegaard, M., Agca, C., Petersen, S. et al. Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor. Purinergic Signalling 13, 545–557 (2017). https://doi.org/10.1007/s11302-017-9582-3

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  • DOI: https://doi.org/10.1007/s11302-017-9582-3

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