Liraglutide Regulates Bone Destruction And Anti-inflammatory In Experimental Periodontitis In Vivo

Background Periodontitis is an infectious disease of periodontal tissue caused by plaque biofilm,which causes destruction of dental support tissues(gum,periodontal ligament,alveolar bone and cementum).If the periodontitis is not treated,it will eventually lead to tooth loss.Periodontitis is the first cause of tooth loss in adults in China.Liraglutide(LIRA)is a new drug for the treatment of type 2 diabetes in the clinic.It has been found that liraglutide not only has the effect of controlling blood glucose,but also has anti-inflammatory and osteoprotective effects.What is more interesting is that The study found that the anti-inflammatory and osteoprotective effects of liraglutide are not dependent on its hypoglycemic effect.Therefore,we speculate whether liraglutide exerts its anti-inflammatory and osteoprotective effects on chronic inflammatory diseases of periodontitis.Objective The purpose of this study was to simulate the periodontitis environment by establishing rats model of experimental periodontitis,and to analyze the effects of liraglutide on the inflammatory and bone effects of periodontitis in vivo.Methods The experiment was divided into four groups: control group(no model of peri odontitis was established,no administration,normal feeding);liraglutide group(LIRA group,model of periodontitis was not established,LIRA 300μg/kg/ Day,i ntraperitoneal injection);periodontitis + saline group(PD+Nacl group,establishe d periodontitis model,given the same amount of normal saline,intraperitonealinjection);periodontitis + liraglutide group(PD+LIRA group,model of periodon titis was established and given LIRA 300 μg/kg/day,intraperitoneal injection).Established male Wister rats periodontitis model by placing ligature and ortho dontic ligation wire around the left maxillary first molar gingival sulcus.One month after the model was established,liraglutide was given to the ligature for one month,and the rats were sacrificed by excessive anesthesia.The gingival index(GI),periodontal pocket depth(PPD)and tooth looseness(TM)of the l eft maxillary first molar were measured.The expression level of serum inflam matory factors TNF-α,IL-6and IL-1β were measured by enzyme-linked immun osorbent assay.Histological analysis(HE staining)to observe the inflammatory cell infiltration and the integrity of periodontal tissue structure;the amount of alveolar bone loss and bone mineral density(BMD),bone volume fraction(BV/ TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separ ation(Tb.Sp)and other changes in bone microstructural parameters in rats maxil la were measured by Micro-CT scanning.Immunohistochemistry staining was us ed to detect the protein levels of RANKL,OPG.Results1.The rats model of experimental periodontitis was successfully established by cotton ligation.2.One month after the administration of liraglutide,compared with the control group and LIRA group by measuring the clinical index of gingival index(GI),periodontal pocket depth(PPD),and tooth looseness(TM).The GI,TM,and PPD of the PD +Nacl group were significantly increased(P<0.01),and the treatment with liraglutide significantly improved the GI and TM indexes(P<0.05).It was also observed by photographing clinical photographs that the degree of periodontal damage was increased in the PD+Nacl group compared with the control group and the LIRA group,and the degree of periodontal damage was reduced in the PD+LIRA group compared with the PD+Nacl group.3.ELISA results: Compared with the control group and the LIRA group,the serumlevels of TNF-α,IL-1β,and IL-6 in the PD+Nacl group were significantly increased(P<0.05),but compared with the PD+Nacl group,the proinflammatory cytokines TNF-α and IL-1β,IL-6 concentrations of the PD+LIRA group were decreased(p<0.05).4.Micro-CT results: Compared with the control group and the LIRA group,the alveolar bone resorption(distance from the alveolar bone crest to the cemento enamel junction)in the PD+Nacl group increased(P<0.01),but compared with PD+Nacl group,there was no significant difference in alveolar bone resorption between PD+LIRA group;compared with control group and LIRA group,BMD,BV / TV,Tb.N,Tb.Th decreased in PD+Nacl group(P<0.01),the value of Tb.Sp increased(P<0.01).Compared with PD+Nacl group,BMD,BV/TV,Tb.N increased and Tb.Sp decreased in PD+LIRA group(p<0.05).5.HE staining results: The area between the left maxillary first molar and the second molar was observed under a light microscope.It was found that in the PD + Nacl group compared with the control group and the LIRA group,the periodontal ligament was destroyed and the cementum was incomplete,alveolar bone destruction and discontinuous,and increased inflammatory cell infiltration.In the PD + LIRA group,periodontal ligament destruction and inflammatory cell infiltration were reduced,alveolar bone loss was significantly reduced,and alveolar bone and cementum integrity were preserved.6.Immunohistochemistry results: Compared with the control group and LIRA group,the periodontal tissues of experimental periodontitis PD + Nacl group had obvious immunostaining on RANK-L,and OPG staining was moderately increased.The OPG staining of rat periodontal tissue in PD + LIRA group was higher than that in PD +Nacl group,and the intensity of RANKL staining was decreased.That is,liraglutide treatment reduced the expression of RANKL in rat periodontal tissues and increased the expression of OPG.Conclusion Liraglutide promotes alveolar bone osteogenesis in experimental periodontitis;andinhibits inflammatory response in experimental periodontitis in rats;this indicates that systemic administration of liraglutide solution is potential treatments for inflammation and bone loss reduction in periodontal disease.This provides a basis for liraglutide to be used as a potential drug for the treatment of periodontitis.