Background and objective
Peri‐implantitis is a plaque‐associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri‐implant mucosa and subsequent progressive loss of supporting bone. Wnt5a is the activating ligand of the non‐canonical Wnt signaling pathways and plays important roles in leukocyte infiltration and cytokine/ chemokine production in inflammatory disorders. Previous studies showed that Wnt5a was significantly up‐regulated in gingival tissues of chronic and aggressive periodontitis. However, the roles and the regulatory mechanisms of Wnt5a in peri‐implantitis are not well known.
Methods
The expression of Wnt5a in gingival tissues collected from 8 healthy implant patients and 8 peri‐implantitis patients was analyzed by Western blotting and immunofluorescence. Porphyromonas gingivalis infected macrophages isolated from the peripheral blood of healthy volunteers were used as an in vitro cellular model of peri‐implantitis. Using neutralizing antibodies, inhibitors and siRNA, the production and roles of Wnt5a in peri‐implantitis were assessed by immunofluorescence, quantitative polymerase chain reaction (RT‐PCR) and Western blotting. Unpaired two‐tailed Student's t test was used to compare qRT‐PCR and Western blotting results. P ≤ .05 was considered statistically significant.
Results
Wnt5a was highly expressed in the gingival tissues of peri‐implantitis patients. Compared to controls, Wnt5a increased in P gingivalis infected macrophages. Wnt5a production in response to P gingivalis infection was dependent on LOX‐1 and TLR4. Compared to controls, Wnt5a knockdown impaired IL‐1β, MCP‐1, and MMP2 production induced by P gingivalis infection.
Conclusion
Our results indicate that Wnt5a is involved in LOX‐1 and TLR4 induced inflammatory signature via inflammatory cytokines production in response to P gingivalis infection. These findings demonstrate that Wnt5a maybe an important component of the host immune response in peri‐implantitis.
Overall, the results of this study provide insight into the essential roles of OPN for IL-1β production and apoptosis in peri-implantitis, as supported by the evidence from the study of patient's PICF and cell culture experiments.
Background and objective:
Dental peri-implantitis, which can be caused by several different microbial factors, is characterized by inflammatory lesions of the surrounding hard and soft tissues of an oral implant. Matrix metalloproteinase 9 (MMP9) is thought to be involved in the pathogenesis of peri-implantitis. However, the regulatory mechanism of MMP9 in peri-implantitis has not been fully elucidated. In this study, we tried to evaluate the regulatory mechanism of MMP9 in peri-implantitis.
Methods:
We collected peri-implant crevicular fluid (PICF) from ten healthy implants and ten peri-implantitis patients and compared their expression level of MMP9. We also cultured macrophages from the peripheral blood of healthy volunteers infected by Porphyromonas gingivalis to reveal the regulatory mechanism of MMP9 in peri-implantitis. Western blot, immunofluorescence staining and quantitative polymerase chain reaction (RT-PCR) were used to better characterize the mechanism of MMP9.
Results:
The expression of MMP9 was up-regulated in peri-implantitis patient PICF and P. gingivalis infected human macrophages. LOX-1, not dectin-1, was found to mediate MMP9 expression in human macrophages with P. gingivalis infection. Expression of Erk1/2 was responsible for infection-induced MMP9 expression. Finally, use of a broad-spectrum metalloproteinase inhibitor impaired LOX-1 expression in infected macrophages.
Conclusion:
Our results demonstrate that MMP9 is involved in dental peri-implantitis and is regulated by LOX-1 and Erk1/2. This LOX-1/MMP9 signaling pathway may represent a potential drug target for peri-implantitis.
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