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

J Steroid Biochem Mol Biol. 2013 May:135:43-50. doi: 10.1016/j.jsbmb.2013.01.008. Epub 2013 Jan 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / drug therapy
  • Animals
  • Blood Glucose / analysis
  • Calcifediol / pharmacology*
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Down-Regulation
  • Glycated Hemoglobin / analysis
  • Janus Kinase 1 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mouth Mucosa / drug effects
  • Mouth Mucosa / metabolism
  • Periodontitis / drug therapy*
  • Periodontitis / etiology
  • Phosphorylation / drug effects
  • Receptors, Calcitriol / metabolism
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Receptors, Calcitriol
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Jak1 protein, mouse
  • Janus Kinase 1
  • Calcifediol