Transcriptomic Alterations in Peri-Implantitis Tissues from Patients with Diabetes, Hypertension, and Osteoporosis: An Exploratory Candidate-Gene Study

Background: Peri-implantitis (PI) is a significant cause of dental implant failure and is characterized by inflammatory destruction of peri-implant tissues with progressive bone loss. Increasing evidence indicates that systemic conditions such as diabetes mellitus (DM), hypertension (HTN), and osteoporosis (OP) may exacerbate peri-implant inflammation by affecting immune regulation and bone metabolism. However, the molecular mechanisms linking these diseases to PI remain insufficiently understood. Methods: Peri-implant gingival tissues were collected from 40 patients treated at Kyungpook National University Dental Hospital and classified into healthy implant (HI) and PI groups. All participants had at least one systemic condition (DM, HTN, or OP). RNA sequencing was performed to identify differentially expressed genes between PI and HI tissues, followed by bioinformatic filtering to identify genes associated with each systemic disease. Selected genes were validated using quantitative reverse transcription–polymerase chain reaction (RT-PCR). Results: Transcriptomic analysis revealed disease-specific gene expression patterns in PI tissues. Ten genes were associated with HTN, fifteen with DM, and four with OP. Validation analyses confirmed consistent upregulation of LCN2, PDK1, NUCB2, MS4A6A, LAMC1, CASP4 , and CLEC3B in the PI group. These genes are involved in inflammatory signaling, apoptosis, and bone remodeling, suggesting a systemic contribution to peri-implant tissue destruction. Conclusions: This transcriptomic analysis demonstrates that systemic diseases such as HTN, DM, and OP modulate PI susceptibility through distinct gene expression alterations, identifying candidate biomarkers for early detection and therapeutic strategies.