Molecular Differences Between Human Periodontitis and Peri-Implantitis Lesions

Objectives: Peri-implantitis is a highly prevalent chronic inflammatory disease affecting dental implants, and a major challenge in contemporary clinical dentistry. Although its clinical phenotype and epidemiology are well documented, there is insufficient knowledge on the molecular mechanisms underlying its development. Specifically, it is unknown whether peri-implantitis is sufficiently distinct from periodontitis with respect to its pathophysiology.
Methods: To systematically investigate the molecular differences between peri-implantitis and periodontitis, we recruited 72 systemically healthy, non-smoking subjects diagnosed with peri-implantitis (32 subjects) and/or periodontitis (40 subjects). A total of 100 peri-implant mucosa/gingival tissue samples were obtained from 50 untreated peri-implantitis lesions [PPD ≥5mm, bone loss ≥3mm, with bleeding-on-probing, mean probing depth 8.01±2.01], and 50 periodontitis lesions [PPD ≥5mm, clinical attachment level ≥4mm, with bleeding-on-probing, mean probing depth 7.96±1.66 mm].

After extraction and quality control of nucleic acids and protein from the samples, sequencing libraries were prepared using the Illumina TruSeq Stranded Total RNA kit and sequenced on an Illumina HiSeq2500 device. A total of 5.7 billion paired-end 125bp reads were collected (56.8 ± 19.5 million/sample).
Raw reads were quality controlled, trimmed, and aligned to the human genome using STAR. Subsequently, genes/exons were counted using featureCounts, and differential expression analyses performed using limma/voom. Functional analyses were performed using Gene Set Enrichment Analysis (GSEA). Selected results were confirmed by qPCR.
Results: The differential expression analysis between 50 pairs of peri-implantitis/periodontitis samples matched with respect to probing depth revealed a high level of similarity between the two conditions. However, despite virtually identical mean disease severity in both groups, the peri-implantitis samples were characterized by increased expression of inflammation- and tissue degradation-related genes and functional groups.
Conclusions: We present evidence that peri-implantitis lesions have distinct molecular profiles from periodontitis lesions, in line with the observed increased progression rates of peri-implant diseases.