Transcriptome-wide Gene Expression Analysis in Peri-implantitis Reveals Candidate Cellular Pathways. (October 2022)

• Record Type: Journal Article
• Authors: Martin, A.; Zhou, P.; Singh, B.B.; Kotsakis, G.A.
• Is Part Of: JDR clinical and translational research. Volume 7:Number 4(2022)
• Page Start: 415
• Page End: 424
• Publication Date: 2022-10
• Subjects: titanium -- phagocytosis -- oxidative stress -- inflammation -- dental implant -- peri-implantitis; Dentistry -- Periodicals; Dental technology -- Periodicals; Oral medicine -- Periodicals; Dentistry; Dental technology; Oral medicine; Periodicals; 617.6005
• DOI: 10.1177/23800844211045297
• Languages: English
• ISSNs: 2380-0844

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.