Wnt5a is involved in LOX-1 and TLR4 induced host inflammatory response in peri-implantitis

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.