The Role Of Slit2 In Periodontitis And Preliminary Study Of Mechanism

BackgroundAccording to reports,periodontitis,as one of the six chronic inflammatory diseases in the world,is a type of high incidence non-specificity characterized by the loss of gingival tissue,periodontal ligament,alveolar bone,cementum and dental support tissue.Chronic infectious diseases are also one of the main reasons leading to the loss of teeth in adults.They cause extremely serious and irreversible damage to teeth,periodontal tissue and alveolar bone.Slit2,a member of neuronal guidance cues,has been reported to regulate inflammation and cancer progression and is a type of secreted glycoprotein that is widely expressed.It was originally found in the nerve tissue of Drosophila.Recent studies have found that Slit2 protein is not only widely expressed in different tissues,but also plays an important regulatory role in tumors,angiogenesis and inflammation.Whether Slit2 affects periodontal inflammation is temporarily unknown,and there is no relevant report.ObjectiveThis study aims to explore the expression pattern of Slit2 in periodontitis and its role in disease progression and bone loss.Material and MethodsGingival tissue of 20 periodontitis patients and 20 healthy controls was obtained.Ligature-induced periodontitis mice-model was developed in Slit2-Tg and wildtype mice.The effect of Slit2 overexpression on inflammation,number of macrophages and alveolar bone loss in periodontitis was analyzed extensively.ResultsIn periodontitis-affected gingival-tissue,Slit2 expression was higher compared to healthy volunteers.Ligature-induced periodontitis enhanced Slit2 expression in mice periodontitis-affected periodontal tissue of wildtype mice.In Slit2-Tg mice periodontitis-affected periodontal tissue,Slit2 expression was higher compared to wildtype mice.Micro-CT scanning and histomorphometric analysis revealed higher cement-enamel-junction to the alveolar-bone-crest(CEJ-ABC)distance and alveolar bone loss in ligature-induced periodontitis Slit2-Tg mice compare to ligature-induced periodontitis wildtype mice.Results from RT-qPCR and ELISA showed a higher expression of TNFα,IL-6,and IL-1β in Slit2-Tg mice periodontitis-affected periodontal tissue compared to wildtype mice.Slit2-Tg mice periodontitis-affected periodontal tissue showed a higher number of osteoclasts and macrophages.And osteoclastogenic markers Acp5,Ctsk,and Nfatc1,but osteogenic markers(Alp,Bglap)remained unchanged.Immunohistochemistry unveils the higher vasculature and infiltration of CD45+inflammatory cell in Slit2-Tg mice periodontitis-affected periodontal tissue.ConclusionSlit2 overexpression in periodontitis intensifies inflammation,number of macrophages,osteoclastogenesis,and alveolar bone loss,suggesting the role of Slit2 on exacerbation of periodontitis and alveolar bone loss.