Mitochondrial dysfunction in peri-implantitis: bioinformatics and machine learning analysis with in vivo experiment

Area of Science:

• Genomics and Bioinformatics
• Oral and Maxillofacial Surgery
• Mitochondrial Biology

Background:

• Peri-implantitis is a significant complication following dental implant placement, characterized by inflammation and bone loss.
• The precise molecular mechanisms underlying peri-implantitis, particularly the role of mitochondrial dysfunction, remain incompletely understood.
• Identifying key genes involved in mitochondrial pathways could reveal novel diagnostic markers and therapeutic targets.

Purpose of the Study:

• To identify mitochondria-related hub genes associated with peri-implantitis using bioinformatics analysis.
• To validate the expression patterns of these identified hub genes in a preclinical rat model of peri-implantitis.
• To explore the potential of these genes as diagnostic biomarkers and therapeutic targets for peri-implantitis.

Main Methods:

• Acquisition and analysis of human peri-implantitis tissue gene expression datasets from the GEO database.
• Cross-referencing with the MitoCarta3.0 database to identify mitochondria-related differentially expressed genes (MitoDEGs).
• Bioinformatic analyses including protein-protein interaction (PPI) networks, Gene Ontology (GO), KEGG pathway analysis, LASSO regression, Boruta algorithm, and ROC curve analysis.
• Establishment of a Sprague-Dawley (SD) rat model of peri-implantitis and validation of hub gene expression using quantitative real-time polymerase chain reaction (qRT-PCR).

Main Results:

• A total of 115 MitoDEGs were identified, with 80 forming a core interaction network.
• Five hub genes (TSPO, THEM5, SARDH, COX4I2, and ACSM1) were selected using machine learning algorithms and demonstrated significant discriminative ability.
• Expression patterns of these five hub genes in the rat peri-implantitis model were consistent with bioinformatics predictions, validating their association with the condition.

Conclusions:

• This study successfully identified five mitochondria-related hub genes (TSPO, THEM5, SARDH, COX4I2, ACSM1) as potential key players in the pathogenesis of peri-implantitis.
• The findings provide novel insights into the molecular mechanisms of peri-implantitis, highlighting the role of mitochondrial pathways.
• These identified hub genes represent promising candidates for further investigation as diagnostic biomarkers and therapeutic targets for peri-implantitis.