Transcriptome-wide Gene Expression Analysis in Peri-implantitis Reveals Candidate Cellular Pathways

A. Martin, P. Zhou, B. B. Singh, G. A. Kotsakis

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Peri-implantitis is a condition resulting in destructive inflammation in the peri-implant soft tissue barrier. Clinically, it demonstrates vast clinical differences to periodontitis that suggest distinct inflammatory mechanisms. Implant-derived titanium particles (i-TiPs) frequently found around diseased implants appear to alter the microenvironment and confer resistance to antibiotic treatments. Studies in orthopedic implants have demonstrated potent inflammatory responses to i-TiPs involving a variety of cell types in aseptic conditions. Nonetheless, the genetic programs of cells surveilling and supporting the peri-implant soft tissue barrier in response to the combined challenges of biomaterial degradation products and oral bacteria are poorly defined. Thus, we studied gene expression specific to oral peri-implant inflammatory disease. Methods: Peri-implant tissues were collected from healthy or diseased implants (N = 10) according to the 2018 classification criteria. Following RNA extraction and purification, a gene-level view of the transcriptome was obtained via a next-generation transcriptome-wide microarray profiling workflow (Clariom S; Applied Biosystems) that covers >20,000 well-annotated genes. A discovery analysis assessed global differential expression of genes and identified pathways in peri-implant health versus disease. Results: Genes involved in the endosomal-lysosomal pathway, such as actin polymerization, were strongly upregulated in diseased tissues (P <.05), proposing increased intracellular activities in response to bacteria and i-TiPs. Cellular respiration pathways involved in oxidative stress were highly transcribed in all peri-implant samples, suggesting that implant-specific factors may trigger a constant state of oxidative stress. Conclusion: Within the limitations of this discovery study, expressive upregulation of genes in the endosomal-lysosomal and oxidative stress pathway suggests that inflammation related to receptor-driven responses to extracellular signals, such as i-TiPs and pathogens, may have a crucial role in peri-implantitis. Results warrant external replication in validation cohorts. Knowledge Transfer Statement: Our findings regarding physiologic processes affected by peri-implantitis could advance knowledge of the mechanisms and consequences of the disease. Understanding the cellular programs that partake in peri-implant inflammation has the potential to translate to novel treatment strategies for patients with peri-implantitis.

Original languageEnglish (US)
JournalJDR Clinical and Translational Research
DOIs
StateAccepted/In press - 2021

Keywords

  • dental implant
  • inflammation
  • oxidative stress
  • peri-implantitis
  • phagocytosis
  • titanium

ASJC Scopus subject areas

  • Dentistry(all)

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