Shu Deng1,2, Yang Hu1,3, Jing Zhou1,3, Yufeng Wang1,4,5, Yuguang Wang6, Sicong Li1,3, Grace Huang1, Cheng Peng2, Anka Hu1, Qing Yu1,3, Xiaozhe Han1,3. 1. Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA. 2. Department of Stomatology, The secondary Hospital of Tianjin Medical University, Tianjin, China. 3. Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. 4. Department of Oral Mucosal Diseases, Ninth People's Hospital, College of Stomatology, Shanghai Jiaotong University School of Medicine, Shanghai, China. 5. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. 6. Center of Digital Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
Abstract
BACKGROUND: The present study was to determine the role of Toll-like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model of Porphyromonas gingivalis-associated ligature-induced peri-implantitis. METHODS: Smooth surface titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in Wild-type (WT) and TLR4-/- (TLR4 KO) mice. Silk ligatures immersed with P. gingivalis were tied around the implants 4 weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses, and gingival mRNA expression levels of cytokines were assessed by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) staining, immunobiological examination and Real-time quantitative polymerase chain reaction, respectively. RESULTS: In both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared with control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared with that in WT mice. Receptor activator of nuclear factor-kappa B ligand /osteoprotegerin (RANKL/OPG) ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL-1β, IFN-γ, and 1L-17 were significantly increased in TLR4 KO mice. CONCLUSION: This study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature-induced peri-implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production.
BACKGROUND: The present study was to determine the role of Toll-like receptor 4 (TLR4) signaling in inflammation and alveolar bone resorption using a murine model of Porphyromonas gingivalis-associated ligature-induced peri-implantitis. METHODS: Smooth surface titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in Wild-type (WT) and TLR4-/- (TLR4 KO) mice. Silk ligatures immersed with P. gingivalis were tied around the implants 4 weeks after the implant placement and confirmation of osteointegration. Two weeks after the ligation, bone resorption, osteoclastogenesis, cellular inflammatory responses, and gingival mRNA expression levels of cytokines were assessed by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) staining, immunobiological examination and Real-time quantitative polymerase chain reaction, respectively. RESULTS: In both WT and TLR4 KO mice, the bone resorption around implants was significantly increased in the P. gingivalis/ligation group compared with control group. In P. gingivalis/ligation group, the levels of bone resorption, TRAP+ cell formation, and gingival CD3+ and CD45+ cell infiltration were significantly decreased in TLR4 KO mice compared with that in WT mice. Receptor activator of nuclear factor-kappa B ligand /osteoprotegerin (RANKL/OPG) ratio was significantly increased after P. gingivalis/ligation treatment in WT mice not in TLR4 KO mice. When comparing the P. gingivalis/ligation group with the respective control group, gingival mRNA expressions of IL-1β, IFN-γ, and 1L-17 were significantly increased in TLR4 KO mice. CONCLUSION: This study suggests that TLR4 mediates alveolar bone resorption in P. gingivalis associated ligature-induced peri-implantitis through regulation of immune B cell infiltration, RANKL/OPG expression ratio, and differential inflammatory cytokine production.
Authors: Sabine Schluessel; Eliza S Hartmann; Miriam I Koehler; Felicitas Beck; Julia I Redeker; Maximilian M Saller; Elif Akova; Stefan Krebs; Boris M Holzapfel; Susanne Mayer-Wagner Journal: Front Immunol Date: 2022-02-11 Impact factor: 7.561