Transcriptome and alternative splicing analyses uncover immune-centric pathogenesis in periodontitis versus...

Area of Science:

• Oral biology
• Molecular pathology
• Biomaterials science

Background:

• Peri-implantitis (PI) presents more severe symptoms and poorer prognosis than periodontitis (PD).
• The precise molecular distinctions underlying their unique pathogeneses remain largely unclear.
• Understanding these differences is crucial for developing targeted therapeutic strategies.

Purpose of the Study:

• To elucidate the molecular differences between peri-implantitis (PI) and periodontitis (PD).
• To identify distinct pathogenetic mechanisms driving bone resorption in PI and PD.
• To provide a molecular basis for differential diagnosis and treatment of these conditions.

Main Methods:

• Establishment of rat models for periodontitis (PD) and peri-implantitis (PI) using silk ligation and bacterial inoculation.
• Confirmation of model induction via micro-CT and HE staining, assessing alveolar bone resorption.
• Transcriptome sequencing to identify differentially expressed genes (DEGs) and alternative splicing (AS) events, with RT-qPCR validation.

Main Results:

• Both PD and PI models showed significant alveolar bone resorption, with PD exhibiting more severe bone loss.
• Transcriptomic analysis revealed distinct molecular profiles: PD-associated DEGs enriched in immune/inflammatory pathways, while PI-associated DEGs focused on keratinization and epithelial barrier function.
• Alternative splicing analysis identified dysregulated splicing events in DNA damage response pathways, with specific gene and variant changes noted in PI.

Conclusions:

• Periodontitis (PD) pathogenesis is characterized by an "inflammation-bone resorption" axis.
• Peri-implantitis (PI) pathogenesis is defined by "epithelial barrier dysfunction-bone resorption."
• These distinct molecular mechanisms offer insights for targeted therapeutic interventions for PI and PD.