1. In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts.
- Author
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McLeod NM, Moutasim KA, Brennan PA, Thomas G, and Jenei V
- Subjects
- Alendronate adverse effects, Bone Density Conservation Agents adverse effects, Cell Proliferation drug effects, Cells, Cultured, Clodronic Acid adverse effects, Coculture Techniques, Fetus, Foreskin cytology, Foreskin drug effects, Humans, Imidazoles adverse effects, Male, Mouth Mucosa cytology, Mouth Mucosa drug effects, Zoledronic Acid, Cell Movement drug effects, Diphosphonates adverse effects, Fibroblasts drug effects, Keratinocytes drug effects
- Abstract
Purpose: Osteonecrosis of the jaws is a potential complication of bisphosphonate (BP) therapy. The underlying mechanisms remain unclear. Although most research has concentrated on the effects of BPs on osteoclast and osteoblast functions, the disease is diagnosed and classified based on of mucosal breakdown, suggesting that oral soft tissues may be involved in its pathogenesis. The aim of this study was to determine the effect of 3 different BP drugs (alendronate, zoledronate, and clodronate) on the function of oral keratinocytes and fibroblasts., Materials and Methods: Human oral keratinocytes (OKF6) and fetal foreskin fibroblasts (HFFF2) were exposed to each drug at several concentrations and the effect on cell proliferation was assessed by counting the viable cells after different lengths of treatment. The effect on cell migration was examined using Transwell migration assays. An organotypic coculture model using keratinocytes and fibroblasts, which recapitulated the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation., Results: The 3 BPs affected the viability and proliferation of OKF6 and HFFF2 cells at concentrations in keeping with their known relative in vitro potencies. There was no effect on cell migration or tissue architecture in organotypic cultures at subtoxic concentrations., Conclusion: The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that BP-related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility., (Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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