Dataset Information

Gingival exudatome dynamics implicates inhibition of the alternative complement pathway in the protective action of the C3 inhibitor Cp40 in non-human primate periodontitis

ABSTRACT: Complement inhibition has been successfully used to treat periodontitis in animal models. However, proteome studies that investigated the role of complement C3 were missing. The objective of this study was to characterize local tissue exudate (“gingival crevicular fluid”; GCF) changes after administration of a potent C3 inhibitor (Cp40, also known as AMY-101) to cynomolgus monkeys (Macaca fascicularis) with established periodontitis. Cp40 was administered locally in the maxillary gingival tissue either once per week (n=5 animals) or three times per week (n=10 animals), for six weeks followed by another six weeks of observation in the absence of treatment. The GCF were collected for liquid chromatography–mass spectrometry analysis (LC-MS/MS).

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Macaca Fascicularis (crab-eating Macaque) (cynomolgus Monkey)

TISSUE(S): Gingival Fluid

SUBMITTER: Kai Bao

LAB HEAD: Nagihan Bostanci

PROVIDER: PXD009502 | Pride | 2018-08-17

REPOSITORIES: Pride

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Publications

Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis.

Bostanci Nagihan N Bao Kai K Li Xiaofei X Maekawa Tomoki T Grossmann Jonas J Panse Christian C Briones Ruel A RA Resuello Ranillo R G RRG Tuplano Joel V JV Garcia Cristina A G CAG Reis Edimara S ES Lambris John D JD Hajishengallis George G

Journal of proteome research 20180829 9

Periodontitis is a prevalent chronic inflammatory disease associated with dysbiosis. Although complement inhibition has been successfully used to treat periodontitis in animal models, studies globally analyzing inflamed tissue proteins to glean insight into possible mechanisms of action are missing. Using quantitative shotgun proteomics, we aimed to investigate differences in composition of inflammatory gingival tissue exudate ("gingival crevicular fluid"; GCF), before and after local administra ...[more]

PMID: 30111112

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Project description:Periodontal regeneration study. Periodontitis is a common chronic inflammatory disease which may lead to tooth loss. The ultimate goal of periodontal therapy is complete regeneration of the tissues lost as a result of periodontitis. However, most regenerative clinical procedures are unpredictable, largely because there is a lack of understanding of how the various tissues comprising the periodontium (gingival epithelium, gingival connective tissue, periodontal ligament, aveolar bone and cementum) interact during the regenerative process. The aim of this study was to investigate the molecular mechanisms that are involved in periodontal regeneration. For this purpose, paired sets of gingival, ligament and regenerating cells were isolated from patients that have been treated for periodontitis via a regenerative surgical procedure. A microarray analysis using the Hu133A Affymetrix arrays was used to identify the genes and pathways that were characteristic of the three different tissues. We have identified over 500 transcripts in global comparison and intrapatient comparisons that were differentially expressed between ligament and gingival samples, and approximately 30 transcripts that characterized the regenerating cell population. By using a functional classification based on Gene Ontology we were able to group the transcripts into 12 groups. Proteases/Protease inhibitors were differentially expressed between the ligament and gingiva highlighting high ECM remodelling activity by gingival cells. On the other hand, ligament cells were shown to have increased protein synthesis by increasing their nucleolar and ribosomal gene complement. We were able to identify 57 various DNA binding proteins, among them were some well characterised transcription factors, transcriptional regulators, including DNA polymerases and transcriptional co-activators. Furthermore, we have also identified changes in expression of their targets in the two tissues. This is the first study to characterise the gene expression profile of periodontal regenerating cells and allowed us to gain valuable insights into the cellular and molecular mechanisms that occur during the regenerative process. We have identified signalling pathways which are consistent with clinical observations of the regenerative properties of gingival and periodontal ligament cells. These pathways provide candidate targets that can be manipulated in order to achieve a superior regenerative clinical outcome.

Dataset Information

Gingival exudatome dynamics implicates inhibition of the alternative complement pathway in the protective action of the C3 inhibitor Cp40 in non-human primate periodontitis

Publications

Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis.

Similar Datasets

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