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PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells

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Abstract

Objectives

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP.

Material and methods

Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis.

Results

ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA.

Conclusions

PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells.

Clinical relevance

At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

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Compliance with ethical standards

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Funding

This study was funded by Pharmascreen Saiotek project (Basque Government).

Conflict of interest

The authors declare the following competing financial interest(s): EA is the Scientific Director of, GO, MZ and MT are scientists at BTI Biotechnology Institute, a dental implant company that investigates in the fields of oral implantology and PRGF-Endoret technology.

Ethical approval

The study was performed following the principles of the Declaration of Helsinki, as revised in 2008 and after approval from the Foundation Eduardo Anitua Institutional Review Board.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Foundation Eduardo Anitua, Jacinto Quincoces, 39, 01007, Vitoria, Spain

    Eduardo Anitua & Gorka Orive

  2. Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain

    Eduardo Anitua, Mar Zalduendo, María Troya & Gorka Orive

Authors
  1. Eduardo Anitua
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  2. Mar Zalduendo
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  3. María Troya
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  4. Gorka Orive
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Corresponding author

Correspondence to Gorka Orive.

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Anitua, E., Zalduendo, M., Troya, M. et al. PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells. Clin Oral Invest 20, 513–521 (2016). https://doi.org/10.1007/s00784-015-1528-y

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  • DOI: https://doi.org/10.1007/s00784-015-1528-y

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