Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activi
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ORIGINAL ARTICLE
Exploring the role of oral microorganisms in the pathogenesis of mucositis by assessing their impact on metabolic activity and reproductive capacity of epithelial cells in vitro Thijs M. Haverman 1 & Alexa M. G. A. Laheij 1,2 Johannes J. de Soet 2 & Frederik R. Rozema 1,4
&
Min Nie 2,3 & Dong M. Deng 2 & Judith E. Raber-Durlacher 1,4 &
Received: 5 November 2019 / Accepted: 17 January 2020 # The Author(s) 2020
Abstract Purpose Clinical and in vitro studies showed selected oral microorganisms to be related to delayed wound healing and ulcerative oral mucositis. However, it is not known whether this effect is due to reduced metabolism and/or the reduced reproductive capacity of epithelial cells. Therefore, we studied the influence of the oral microorganisms Porphyromonas gingivalis, Candida glabrata, and Candida kefyr on cell metabolism and reproductive capacity of oral epithelial cells, aimed to further unravel the pathogenesis of oral mucositis. Methods Oral epithelial cells were exposed to different concentrations of P. gingivalis, C. glabrata, and C. kefyr as monoinfections or mixed together. An MTT assay was performed to determine the effect on cell metabolism. A clonogenic assay was used to study the effect on the reproductive capacity of oral epithelial cells. Results The metabolism of oral epithelial cells was reduced when the microorganisms were present in high concentrations: P. gingivalis at a multiplicity of infection (MOI) of 1000 and the Candida spp. at MOI 100. No statistical difference was observed in the ability of a single epithelial cell to grow into a colony of cells between control and P. gingivalis, C. glabrata, and C. kefyr, independent of the concentrations and combinations used. Conclusion P. gingivalis, C. glabrata, and C. kefyr lowered the metabolic activity of oral epithelial cells in high concentrations, yet they did not influence the reproductive capacity of epithelial cells. Their impact on ulcerative oral mucositis is likely due to an effect on the migration, proliferation, and metabolism of epithelial cells. Keywords Oral mucositis . Oral epithelial cells . Wound healing . P. gingivalis . Candida spp. . Clonogenic assay
Introduction
* Alexa M. G. A. Laheij [email protected] 1
Department of Oral Medicine, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and the Vrije Universiteit Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
2
Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and the Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
3
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
4
Department of Oral- and Maxillofacial Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Cancer patients undergoing radiotherapy to the head and neck area or receiving high dose chemotherapy often suffer from severe oral mucositis [23]. Ulcerative oral mucositis is characterized by the lo
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