Genetic Analysis of Exacerbated Healing Responses after Periodontal Therapy due to Type 2 Diabetes: Clinical and in vivo Studies

Abstract Background This study aims to investigate the mechanisms underlying the exacerbated healing response by diabetes after periodontal therapy. Methods Zucker 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. Results Ligation-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 an enrichment of downregulated genes involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPARα and PPARγ were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, less probing depth reduction and significantly downregulated expression of PPARα and PPARγ were detected in the residual periodontal pocket of the T2D group compared with those of the control group. Conclusions Downregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.