title: Modulation of Wnt/β-catenin signaling attenuates periapical bone lesions.
abstract: 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.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: L
authors.initials: L
authors.lastname: Zheng
mesh_terms: D016301:Alveolar Bone Loss / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D018929:Cell Culture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008336:Mandibular Diseases / Q000473:pathology / Q000503:physiopathology; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D015675:Osteocalcin / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010485:Periapical Periodontitis / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D016966:Porphyromonas gingivalis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D060509:Wnt3A Protein / Q000494:pharmacology; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C493717:Runx2 protein, rat; C495181:Sp7 protein, rat; D014157:Transcription Factors; D060509:Wnt3A Protein; D015675:Osteocalcin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
keywords: BMMSCs; LPS; Wnt3a; osteoblast; osteogenesis; β-catenin