The Effect Of Liraglutide On The Anti-inflammatory And Osteogenic Of Periodontitis In Diabetic Rats

BackgroundPeriodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth.Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation.A number of studies have demonstrated the potential beneficial role for GLP-1 receptor agonists(GLP-1RAs)in the skeleton metabolism in diabetic rodents and patients.Novel anti-diabetic Liraglutide is a type of glucagon-like-peptide 1 receptor agonist,which has shown new functions including Anti-inflammatory and osteoprotective effects.Liraglutide administration displays an anabolic effect on bone.This study evaluates the effects of Liraglutide administration on alveolar bone loss and inflammation changes in rats with diabetes mellitus and ligature-induced periodontitis.ObjectiveThis study explored the potential therapeutic effect of LIRA on diabetic periodontitis in rats.By establishing a rat model of diabetic periodontitis,the anti-inflammatory effect of LIRA on diabetic periodontitis and the relationship between osteogenic differentiation and inflammatory factors were analyzed in vivo,which provided theoretical basis and therapeutic drugs for clinical treatment of diabetic periodontitis.MethodsForty-six male Wistar rats were randomly divided into five groups:(1)Control group(no ligated saline placebo and STZ injection),(2)a LIRA group(Liraglutide administration without ligature and STZ injection),(3)an DP+NaCl group(saline placebo with ligature and STZ injection),and(4)an DP+LIRA group(Liraglutide administration with ligature and STZ injection).After successful establishment of diabetic periodontitis rats by periodontal ligation and STZ injection,Liraglutide wasadministered at 300 ?g/kg per dose one times a day for 28 days.Subsequently,all rats were sacrificed,all rats were executed to take blood samples and cut their maxillary bones for testing.The levels of inflammatory cytokines(IL-6,TNF-alpha and IL-1beta)and Calcitonin in serum were detected by ELISA kit.The morphological changes of periodontal tissues were observed by HE staining,the absorption of alveolar bone and its ultrastructural changes were observed by histomorphology and Micro-CT,and the expression of RANKL and OPG in alveolar bone was detected by immuohistochemistry.The expression of Runx2 and ALP mRNA in gingival epithelium was detected by qRT-PCR.Results1.Establishment of the model of diabetic periodontitis: Compared with the control group,the rats in the experimental group had higher fasting blood glucose,higher glucose tolerance and higher periodontal clinical indexes(p<0.05).The rats with diabetic periodontitis were successfully established by attachment loss,alveolar bone resorption and tooth loosening.2.The results of ELISA showed that the serum inflammatory factors IL-6,TNF-?and IL-1? in the DP+LIRA group were compared with the DP+NaCl group,the secretion levels were significantly decreased(p<0.05),and the secretion of calcitonin was significantly increased(p<0.05).3.Histomorphology and Micro-CT results showed that compared with DP+NaCl group,the absorption of alveolar bone in DP+LIRA group was significantly reduced,and the microstructure of alveolar bone was significantly improved(p<0.05).4.HE staining and immunohistochemistry showed that the DP+LIRA group had severe inflammation in the periodontal tissues of the DP+NaCl group,and the ratio of NF-?B ligand(RANKL)/osteoprotegerin(OPG)was significantly decreased(p<0.05).5.qRT-PCR results showed that the expression of Runx2 and ALP in LIRA group was higher than that in Control group,the expression of Runx2 and ALP in DP+LIRA group was higher than that in DP+NaCl group(p<0.05).Conclusions1.Successful establishment of diabetic periodontitis rat model.2.LIRA inhibited the secretion of IL-6,TNF-a and IL-1? in serum and promoted the secretion of Calcitonin.3.Systemic administration of LIRA effectively reduced alveolar bone resorption in STZ-induced diabetic rats and improved the inflammatory response ofexperimental periodontitis in diabetic rats,and promote the osteogenic differentiation of alveolar bone to a certain extent.