Denervation Effectively Aggravates Rat Experimental Periodontitis

Periodontitis is a prevalent oral inflammatory disease characterized by the irreversible alveolar bone loss,shrinkage of the gingival tissues and deep periodontal pockets(1).Numerous factors such as inflammatory mediators,growth factors,chemotactic factors and neuropeptides get involved in the deterioration of periodontal tissues.Nerve and neuropeptidesshould be potentially crucial factors in the process of periodontal inflammation through direct and/or indirect way.Hence,we conducted the study firstly by denervation animal model to investigate the contribution of the inferior alveolar nerve in the experimental periodontitis and lay a theoretical foundation for future inflammation regulation and periodontal tissue regeneration.TNF-a and IL-1?,as two of the important pro-inflammatory mediators,were significantly up-regulated in the process of periodontitis,which are actively involved in jeopardizing periodontal tissues by affecting the activities of leukocytes,oteoclasts and collagenolytic enzyme MMPs to mediate alveolar bone resorption and collagen destruction.Recent studies demonstrate that host is predominantly responsible for tissue destruction in periodontal inflammatory process,which lead to the clinical symptoms of periodontitis.Host response can provide the potential for reducing tissue destruction by improving excessively elevated inflammatory process to enhance opportunities for periodontal stability and repair.Nervous system is an important part of the host response.Accordingly,innervation or denervation may also get involved in the host response modulation.We have previously shown that innervation governs periodontal bone regeneration and repair process,denervation results in excessive bone resorption and delays periodontal defect repair.However,Nerve and its related factors in the occurrence and development of periodontitis still require further investigation.Denervation is a useful supplement of nerve and innervation researches.Therefore,we established a rat model of inferior alveolar nerve transection combined ligature-induced periodontitis to elucidate the effects of denervation on rat experimental periodontitis.Material and Methods:64 Wistar rats were distributed to the four groups randomly:Ligation(L)group,Denervation(D)group,Ligation+Denervation(LD)group and Normal group(N)as control.A ligation-inducing rat experimental periodontitis model was established in the L and LD groups.Rats in the D and LD groups also underwent the transection of the right inferior alveolar nerve simultaneously.Four weeks after operation,the mandibles were taken out for micro-CT analysis.Osteoclast number was observed through TRAP staining.The gingival tissues around the first molars were homogenized and measured by ELISA for IL-1? and TNF-a.Collagen fiber were observed using Picro-Sirius Red staining.NF-?B p65 and I?B? phosphorylation and OPG/RANKL ratio in the gingival tissues were detected by western blotting.Results:Denervation strongly promoted ligature-induced alveolar bone loss in the LD group.The alveolar bone loss of the LD group was significantly increased comparing with the ligation group.Furthermore,denervation aggravated trabecular bone breakdown in the bone specific parameters,including percent bone area,trabecular thickness and bone mineral density.Increased TRAP-positive osteoclasts were detected in alveolar bone of the LD group.More seriously collagen fiber destructions and increased expressions of IL-1? and TNF-a were found in the LD group.NF-?B p65 and I?B?phosphorylation were also significantly upregulated in the LD group.OPG/RANKL ratio in the gingival extracts was markedly decreased in the LD group comparing with the L group.Decreased OPG/RANKL ratio was observed in the D group,comparing with the N group.Conclusion:Denervation effectively aggravates ligature-induced rat periodontitis by NF-?B signaling pathway for excessive production of IL-1? and TNF-? and increased osteoclasts for decreased OPG/RANKL ratio.The rat model of inferior alveolar nerve transection combined ligature-induced periodon0.titis provides an animal model to further observed the change of nerve related factors in the occurrence and development of periodontitis,so as to select positive nerve related factors to regulate inflammation and promote periodontal regeneration in future.