25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice

Vitamin D has been known to be closely associated with diabetes and periodontitis while the underlying mechanism has yet to be clarified. The present study aimed to discover the effect of 25-hydroxyvitamin D3 (25-OHD3) on glycemic control and periodontal health in mice with periodontitis superimposed on experimental diabetes (known as diabetic periodontitis). We showed that 25-OHD3 intraperitoneal injection attenuated diabetic periodontitis by reducing serum fasting blood glucose, glycosylated hemoglobin and TNF-α levels, which led to decreased alveolar bone loss. Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. Our study extends the previous findings on the regulation of diabetes with periodontitis, and may also provide a potential therapy for the patients with this disease.

► 25-OHD3 attenuates periodontits superimposed on diabetes in mice.
► 25-OHD3 inhibits TLR4 expression of inflamed gingival epithelium.
► 25-OHD3 does not regulate gingival epithelial STAT1 expression or phosphorylation.
► 25-OHD3 suppresses gingival JAK1/STAT3 signaling in diabetic periodontitis.