Genetic analysis of impaired healing responses after periodontal therapy in type 2 diabetes: Clinical and in vivo studies

ObjectiveThis study aims to investigate the mechanisms underlying the impaired healing response by diabetes after periodontal therapy.BackgroundOutcomes of periodontal therapy in patients with diabetes are impaired compared with those in patients without diabetes. However, the mechanisms underlying impaired healing response to periodontal therapy have not been sufficiently investigated.Materials and MethodsZucker diabetic fatty (ZDF) and lean (ZL) rats underwent experimental periodontitis by ligating the mandibular molars for one week. The gingiva at the ligated sites was harvested one day after ligature removal, and gene expression was comprehensively analyzed using RNA-Seq. In patients with and without type 2 diabetes (T2D), the corresponding gene expression was quantified in the gingiva of the shallow sulcus and residual periodontal pocket after non-surgical periodontal therapy.ResultsLigation-induced bone resorption and its recovery after ligature removal were significantly impaired in the ZDF group than in the ZL group. The RNA-Seq analysis revealed 252 differentially expressed genes. Pathway analysis demonstrated the enrichment of downregulated genes involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPAR alpha and PPAR gamma were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, probing depth reduction was significantly less in the T2D group than control. Significantly downregulated expression of PPAR alpha and PPAR gamma were detected in the residual periodontal pocket of the T2D group compared with those of the control group, but not in the shallow sulcus between the groups.ConclusionsDownregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.