title: 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice.
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.
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 3rd Section S Renmin Road, Chengdu 610041, PR China.
authors: Qi
authors: Q
authors: Wang
authors: Hao
authors: H
authors: Li
authors: Honghui
authors: H
authors: Xie
authors: Min
authors: M
authors: Fu
authors: Bin
authors: B
authors: Guo
authors: Yi
authors: Y
authors: Ding
authors: Wei
authors: W
authors: Li
authors: Haiyang
authors: H
authors: Yu
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002112:Calcifediol / Q000494:pharmacology*; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D015536:Down-Regulation; D006442:Glycated Hemoglobin / Q000032:analysis; D053613:Janus Kinase 1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy* / Q000209:etiology; D010766:Phosphorylation / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002112:Calcifediol; D006442:Glycated Hemoglobin; D053613:Janus Kinase 1; D018167:Receptors, Calcitriol; D050796:STAT3 Transcription Factor; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C494087:Stat3 protein, mouse; C493487:Tlr4 protein, mouse; C507905:Jak1 protein, mouse