Wnt4 Attenuates Peridontal Bone Loss in Murine Periodontitis Model

Objectives: Periodontitis is a bacterial infection-induced inflammatory response leading to the destruction of connective tissues and underlying alveolar bone, culminating in the loss of tooth support. Conventional treatment for periodontitis focuses on mechanical debridement or biochemical suppression of microbial pathogens such as porphyromonas gingivalis (PG) and fusobacterium nucleatum (FN). However, emerging evidence suggests that resolution of periodontal inflammation could represent a novel and improved approach for treating periodontal diseases. Previously we found that growth factor Wnt4 could protect against osteoporotic and inflammatory bone loss in mice, via suppresion of osteoclasts and attenuation of NF-κB signaling in the bone marrow. The objective of this study is to evaluate if Wnt4 could attenuate periodontal inflammation and bone loss in a murine periodontitis model.
Methods: We generated Wnt4 transgenic mice that overexpressed Wnt4 specifically in osteoblasts/odontoblasts. Periodontal bone loss was induced in wild type (WT) and Wnt4 mice (n=8 per group) through inoculation of PG and FN via oral gavage for 2 weeks. 8 weeks following bacterial infection, alveolar bone loss in the mandibles were evaluated by microcomputer tomography and histology. Infiltration of neutrophils and macrophages, markers of periodontal inflammation and NF-κB activation in the periodontium were evaluated via immunohistochemistry. Presence of osteoclasts in the periodontium was assessed by TRAP staining.
Results: Preliminary results demonstrated that periodontal bone loss was effectively attenuated in Wnt4 mice, with significant reduction of inflammatory cell infiltration as well as expression of Mmp8 and Mmp13. While microbial infection enhanced osteoclasts in the periodontium of WT mice, this induction was significantly suppressed in Wnt4 mice. Consistently, expression of NF-κB target genes p65 and Cox2 were markedly suppressed in Wnt4 periodontium.
Conclusions: Increased secretion of Wnt4 attenuated NF-κB mediated periodontal inflammation and osteoclast formation to slow down alveolar bone loss, thus promising a potential therapeutic target for treatment of periodontitis.