Interaction between the Wnt/β‐catenin signaling pathway and the EMMPRIN / MMP ‐2, 9 route in periodontitis

Background and Objectives In periodontitis, the Wnt/β‐catenin signaling pathway is related to the metabolism of the alveolar bone; further, extracellular matrix metalloproteinase inducer ( EMMPRIN ) expression is correlated with matrix metalloproteinases ( MMP s) expression and inflammation severity. The aim of this study was to perform a preliminary investigation of the interaction between the Wnt/β‐catenin signaling pathway and the EMMPRIN / MMP s route in periodontitis. Material and Methods Chronic periodontitis and healthy gingival tissues were obtained to detect the expression of Wnt3a, β‐catenin, EMMPRIN and MMP ‐2, 9 by using immunohistochemical analysis. The human immortalized oral epithelial cell/human gingival fibroblast direct co‐culture model was treated with 10 μg/ mL Porphyromonas gingivalis lipopolysaccharide (Pg. LPS ). Anti‐ EMMPRIN antibody was used to block the effect of EMMPRIN . Dickkopf‐1 ( DKK ‐1) and Wnt3a were used as the inhibitor and activator of the Wnt/β‐catenin signaling pathway, respectively. Immunofluorescence was performed to visualize the localization of β‐catenin and EMMPRIN . Expression of the EMMPRIN , MMP ‐2, 9 and Wnt pathway's components was confirmed by western blotting and quantitative real‐time polymerase chain reaction. Results Higher levels of Wnt3a, β‐catenin, EMMPRIN and MMP ‐2, 9 were observed in chronic periodontitis gingival tissues compared with controls. Pg. LPS significantly enhanced β‐catenin, p‐ GSK ‐3β, EMMPRIN and MMP ‐2, 9 inductions in the human immortalized oral epithelial cell/human gingival fibroblast co‐culture model. Anti‐ EMMPRIN antibody markedly reduced the expression of MMP ‐2, 9 only in the presence of Pg. LPS . Co‐expression of β‐catenin and EMMPRIN was detected in the co‐culture model. DKK ‐1 inhibited Wnt pathway, but upregulated the EMMPRIN / MMP ‐2, 9 routes. In contrast, activating Wnt pathway by Wnt3a repressed the EMMPRIN / MMP ‐2, 9 routes. The promotion effect of DKK ‐1 on MMP ‐2, 9 expressions was partially inhibited by the anti‐ EMMPRIN antibody. In addition, anti‐ EMMPRIN antibody led to a drastic decrease in β‐catenin and p‐ GSK ‐3β. Conclusion In periodontitis, EMMPRIN regulates MMP ‐2, 9 expressions, the activation of Wnt/β‐catenin signaling pathway downregulates the EMMPRIN / MMP ‐2, 9 routes and the blockade of EMMPRIN attenuates Wnt/β‐catenin signaling pathway.