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In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts

In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts
In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts
Introduction
Osteonecrosis of the jaws is a potential complication of bisphosphonate therapy. The underlying mechanism(s) remain unclear. While most research has concentrated on the effects of bisphosphonates on osteoclast and osteoblast function, the disease is diagnosed and classified on the basis of mucosal breakdown, suggesting that oral soft tissues may be involved in its pathogenesis.

Aims
To determine the effect of three different bisphosphonate drugs (aledronate, zoledronate and clodronate) on the function of oral keratinocytes and fibroblasts.

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 co-culture model using keratinocytes and fibroblasts, which recapitulates the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation.

Results
The three bisphosphonates 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.

Discussion
The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that bisphosphonate related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility.
0278-2391
McLeod, Niall
614fd120-05fb-4250-b9e6-57ecf206ecdb
Moutasim, Karwan A.
af7dd711-f6df-44f7-8c57-052bf15303af
Brennan, Peter
a78880d9-9740-4d33-adb1-8ca8f65dea58
Thomas, Gareth J
2ff54aa9-a766-416b-91ee-cf1c5be74106
Jenei, Veronika
04d82852-7d30-458a-bc0b-f00ae6c5dd52
McLeod, Niall
614fd120-05fb-4250-b9e6-57ecf206ecdb
Moutasim, Karwan A.
af7dd711-f6df-44f7-8c57-052bf15303af
Brennan, Peter
a78880d9-9740-4d33-adb1-8ca8f65dea58
Thomas, Gareth J
2ff54aa9-a766-416b-91ee-cf1c5be74106
Jenei, Veronika
04d82852-7d30-458a-bc0b-f00ae6c5dd52

McLeod, Niall, Moutasim, Karwan A., Brennan, Peter, Thomas, Gareth J and Jenei, Veronika (2013) In vitro effect of bisphosphonates on oral keratinocytes and fibroblasts. Journal of Oral and Maxillofacial Surgery. (doi:10.1016/j.joms.2013.08.007).

Record type: Article

Abstract

Introduction
Osteonecrosis of the jaws is a potential complication of bisphosphonate therapy. The underlying mechanism(s) remain unclear. While most research has concentrated on the effects of bisphosphonates on osteoclast and osteoblast function, the disease is diagnosed and classified on the basis of mucosal breakdown, suggesting that oral soft tissues may be involved in its pathogenesis.

Aims
To determine the effect of three different bisphosphonate drugs (aledronate, zoledronate and clodronate) on the function of oral keratinocytes and fibroblasts.

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 co-culture model using keratinocytes and fibroblasts, which recapitulates the morphology of the oral mucosa, was used to assess the effect of the drugs on epithelial stratification and differentiation.

Results
The three bisphosphonates 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.

Discussion
The lack of effect of these drugs on cell migration below concentrations known to affect cell viability suggests that bisphosphonate related osteonecrosis is not caused through suppression of keratinocyte or fibroblast motility.

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More information

e-pub ahead of print date: 14 August 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 360300
URI: http://eprints.soton.ac.uk/id/eprint/360300
ISSN: 0278-2391
PURE UUID: 44793215-5df4-43c0-92d6-95df8d4fbe83

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Date deposited: 03 Dec 2013 16:03
Last modified: 14 Mar 2024 15:35

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Contributors

Author: Niall McLeod
Author: Peter Brennan
Author: Gareth J Thomas
Author: Veronika Jenei

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