Investigation of mitochondria-endoplasmic reticulum contact proteins in the pathogenesis of Periodontal disease

Objective: Mitochondria–endoplasmic reticulum contact sites (MERCs) are involved in essential cellular processes such as calcium signaling and apoptosis regulation. This study aimed to investigate the levels of MERC-related proteins (VAPB, PTPIP51, IP3R, GRP75, and VDAC) in saliva, gingival crevicular fluid (GCF), and gingival tissue of individuals with varying periodontal conditions. Additionally, it evaluated levels of reactive oxygen species (ROS), calcium, and caspase-3 (CASP3) to explore the relationship between MERC proteins and oxidative stress, calcium metabolism, and apoptosis. Materials and Methods: Forty-eight systemically healthy participants were divided into three groups: periodontally healthy (n=16), gingivitis (n=16), and periodontitis (n=16). Protein levels in saliva and GCF were measured using ELISA. Gingival tissue samples were obtained from 60 individuals across the same groups for gene expression analysis using RT-qPCR. Results: In periodontitis patients, total levels of VAPB, GRP75, VDAC, CASP3, and ROS in GCF were elevated, whereas PTPIP51 was decreased (p<0.05). However, the concentrations of all measured markers in GCF were significantly reduced (p<0.05). In gingival tissue, gene expressions of PTPIP51, IP3R, GRP75, CASP3, ROS, and ATP2B1 were upregulated, while VAPB and VDAC were downregulated (p<0.05). GCF CASP3, calcium, and ROS levels were negatively correlated with PTPIP51 but positively correlated with GRP75 (p<0.05). Conclusion: MERC-related proteins VAPB, GRP75, VDAC, and PTPIP51 may play a role in the pathogenesis of periodontititis. PTPIP51 and GRP75 may be associated with apoptosis, oxidative stress, and calcium mechanisms in the progression of periodontal disease. Keywords: MERC, Periodontitis, Gingivitis, Mitochondria, ER