Role of Toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis vs.Periodontitis

【作者】 杨建军； 于新波； Han Xiaozhe；

【Author】 Han Xiaozhe;The Forsyth Institute;

【机构】 青岛大学附属医院； The Forsyth Institute；

【摘要】 Objective and background:Peri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic signs.Toll-like receptor 2(TLR2),one of the key pathogen recognition receptors in the innate immune system,plays an important role in the progress of periodontitis.However,the role of TLR2 in peri-implantitis remains unclear.The objective of this study was to investigate the role of TLR2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it to ligature-induced periodontitis.Methods:Smooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of Wild Type(WT) and TLR2 knockout(KO) mice 6 weeks after tooth extraction.Silk ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant placement.Bone loss and inflammation around the implants and maxillary second molars were analyzed by micro-computed tomography(micro-CT) and histology and TRAP staining respectively 2 weeks after ligation.Gingival mRNA expressions of pro-inflammatory cytokines(IL-1β,TNF-α),anti-inflammatory cytokine(IL-10)and osteoclastogenesis-related cytokines(RANKL,OPG) were evaluated using real-time quantitative PCR(RT-qPCR).Results:Success Rate(SR) of Implant osseointegration was significantly greater in TLR2 KO mice(85.71%) when compared to WT mice(53.66%)(p=0.0125).Micro-CT revealed significantly decreased bone loss in TLR2 KO mice as compared to WT mice(p= 0.0094) in peri-implantitis.Gingival mRNA expressions of IL-1 b(p= 0.0055),TNF-α(p= 0.01) and IL-10(p= 0.0019) was significantly elevated in the peri-implantitis tissues of WT mice,but not in TLR2 KO mice,as compared to controls.However,the gingival mRNA ratios of RANKL/OPG in peri-implant tissues were significantly up-regulated in both WT(p=0.0488) and TLR2 KO mice(p= 0.0314).Ligature-induced periodontitis exhibited the similar patterns in bone loss and inflammatory cytokine profile except that IL-10 level was elevated(p= 0.0114) whereas RANKL/OPG ratio was not elevated(p=0.9755) in TLR2 KO mice compared to control.Histological findings showed increased TRAP-positive cells and infiltrated inflammatory cells presented in ligature-induced peri-implantitis in both WT(p<0.01) and TLR2 KO mice(p<0.05),both of which were significantly greater in WT mice than that in TLR2 KO mice.Conclusion:This study suggests that TLR2 mediates bone loss in both peri-implantitis and periodontitis.However,different molecular features may exist in the pathogenesis of the two diseases.更多还原

【Abstract】 Objective and background:Peri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic signs.Toll-like receptor 2(TLR2),one of the key pathogen recognition receptors in the innate immune system,plays an important role in the progress of periodontitis.However,the role of TLR2 in peri-implantitis remains unclear.The objective of this study was to investigate the role of TLR2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it to ligature-induced periodontitis.Methods:Smooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of Wild Type(WT) and TLR2 knockout(KO) mice 6 weeks after tooth extraction.Silk ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant placement.Bone loss and inflammation around the implants and maxillary second molars were analyzed by micro-computed tomography(micro-CT) and histology and TRAP staining respectively 2 weeks after ligation.Gingival mRNA expressions of pro-inflammatory cytokines(IL-1β,TNF-α),anti-inflammatory cytokine(IL-10)and osteoclastogenesis-related cytokines(RANKL,OPG) were evaluated using real-time quantitative PCR(RT-qPCR).Results:Success Rate(SR) of Implant osseointegration was significantly greater in TLR2 KO mice(85.71%) when compared to WT mice(53.66%)(p=0.0125).Micro-CT revealed significantly decreased bone loss in TLR2 KO mice as compared to WT mice(p= 0.0094) in peri-implantitis.Gingival mRNA expressions of IL-1 b(p= 0.0055),TNF-α(p= 0.01) and IL-10(p= 0.0019) was significantly elevated in the peri-implantitis tissues of WT mice,but not in TLR2 KO mice,as compared to controls.However,the gingival mRNA ratios of RANKL/OPG in peri-implant tissues were significantly up-regulated in both WT(p=0.0488) and TLR2 KO mice(p= 0.0314).Ligature-induced periodontitis exhibited the similar patterns in bone loss and inflammatory cytokine profile except that IL-10 level was elevated(p= 0.0114) whereas RANKL/OPG ratio was not elevated(p=0.9755) in TLR2 KO mice compared to control.Histological findings showed increased TRAP-positive cells and infiltrated inflammatory cells presented in ligature-induced peri-implantitis in both WT(p<0.01) and TLR2 KO mice(p<0.05),both of which were significantly greater in WT mice than that in TLR2 KO mice.Conclusion:This study suggests that TLR2 mediates bone loss in both peri-implantitis and periodontitis.However,different molecular features may exist in the pathogenesis of the two diseases.更多还原