Proteomanalyse parodontaler Zellen in Kultur mit Aggregatibacter actinomycetemcomitans und Eikenella corrodens

Proteomic analysis of periodontal cells in culture with Aggregatibacter actinomycetemcomitans and Eikenella corrodens

by Boris Schminke
Doctoral thesis
Date of Examination:2022-05-18
Date of issue:2022-05-12
Advisor:PD Dr. Philipp Kauffmann
Referee:PD Dr. Philipp Kauffmann
Referee:Prof. Dr. Hassan Dihazi
Persistent Address: http://dx.doi.org/10.53846/goediss-9230

 

 

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Abstract

English

The periodontium is formed by gingiva, root cementum, PDL and alveolar bone. It is responsible for elastic anchorage of the tooth in the alveolar bone, proprioception during mastication, speech, and protection of adjacent structures from the oral microbiome. The chronic inflammatory disease of the periodontium is defined as PA and leads to irreversible destruction of the periodontium without therapy. PA is now the leading cause of tooth loss. The molecular mechanisms during the pathogenesis of PA in human periodontal cells at the proteome level have not been investigated. The aim of this work is to perform a proteomic analysis by label-free high-resolution mass spectrometry of all cells of the periodontium established here in pure culture and in culture with the PA-associated bacteria Aggregatibacter actinomycetemcomitans and Eikenella corrodens. For the first time, a specific protein profile can be assigned to each cell line for characterization. As expected, large differences were observed in the proteome of GK from the ectodermal lineage compared to the group consisting of OZAK, PDLF and ZZ of mesodermal origin. This characteristic was maintained during bacterial culture. In summary, cell-specific changes of immunoregulatory proteins show activation of the immune system in GK +, OZAK +, PDLF + and ZZ +. In a further step, there is a disturbance of cell interactions and the EZM, which can be interpreted as typical signs of inflammation. An essential component of the ribosome is elongation factor 2, which shows a reduction across all cell lines due to bacterial irritation. It is therefore a potential objective for targeted local therapy to maintain protein biosynthesis during PA. Another interesting approach could be the protection of collagens as the basic structure of the EZM throughout the periodontium at the level of mRNA by substitution of vimentin, which is produced in a reduced manner during culture. The generated results cannot be fully translated to in vivo PA, but the established cell lines and reproducible bacterial irritation are promising for future in vitro PA research to advance therapeutic approaches as well.
Keywords: Proteomics; Periodontitis; periodontal cells
 
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