Modulation of Wnt/β-catenin signaling attenuates periapical bone lesions

Wnt/β-catenin signaling plays an important role in bone biology. The present study investigated the involvement of Wnt/β-catenin signaling in rat periapical bone destruction and whether lithium chloride (LiCl), a glycogen synthase kinase-3β (GSK-3β) inhibitor, promotes bone restoration. Rat bone marrow mesenchymal cells (BMMSCs) treated with Porphyromonas gingivalis lipopolysaccharide (Pg LPS) showed decreased osteogenic potential through inhibited Wnt/β-catenin signaling as quantified by Western blot, immunofluorescence, and luciferase reporter assay. Transient Wnt3a treatment in vitro partially restored mineralization and Runx2/Osx and osteocalcin expression in cultures with Pg LPS-induced osteogenic arrest. Prolonged Wnt3a treatment impaired osteogenic commitment. X-ray microtomography showed dramatically enhanced periapical bone formation in rats gavage-fed with LiCl for 2 wks, while continuous LiCl treatment for 4 wks impaired periapical bone healing. LiCl treatment also increased GSK-3β phosphorylation and osteocalcin expression in periapical tissue. Collectively, these results indicate that Wnt/β-catenin has dichotomous functions in bone homeostasis. Modulation of this signaling pathway by LiCl may be a potential therapeutic option for bone destruction in endodontic disease.