title: Wnt signaling regulates homeostasis of the periodontal ligament.
abstract: OBJECTIVE
  In health, the periodontal ligament maintains a constant width throughout an organism's lifetime. The molecular signals responsible for maintaining homeostatic control over the periodontal ligament are unknown. The purpose of this study was to investigate the role of Wnt signaling in this process by removing an essential chaperone protein, Wntless (Wls), from odontoblasts and cementoblasts, and observing the effects of Wnt depletion on cells of the periodontal complex.
  
  
  METHODS
  The Wnt responsive status of the periodontal complex was assessed using two strains of Wnt reporter mice: Axin2(LacZ/+) and Lgr5(LacZ/+) . The function of this endogenous Wnt signal was evaluated by conditionally eliminating the Wntless (Wls) gene using an osteocalcin Cre driver. The resulting OCN-Cre;Wls (fl/fl) mice were examined using micro-computed tomography and histology, immunohistochemical analyses for osteopontin, Runx2 and fibromodulin, in-situ hybridization for osterix and alkaline phosphatase activity.
  
  
  RESULTS
  The adult periodontal ligament is Wnt responsive. Elimination of Wnt signaling in the periodontal complex of OCN-Cre;Wls(fl/fl) mice resulted in a wider periodontal ligament space. This pathologically increased periodontal width is caused by a reduction in the expression of osteogenic genes and proteins, which results in thinner alveolar bone. A concomitant increase in fibrous tissue occupying the periodontal space was observed, along with a disruption in the orientation of the periodontal ligament.
  
  
  CONCLUSIONS
  The periodontal ligament is a Wnt-dependent tissue. Cells in the periodontal complex are Wnt responsive, and eliminating an essential component of the Wnt signaling network leads to a pathological widening of the periodontal ligament space. Osteogenic stimuli are reduced, and a disorganized fibrillary matrix results from the depletion of Wnt signaling. Collectively, these data underscore the importance of Wnt signaling in homeostasis of the periodontal ligament.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA; Department of Orthodontics, School of Dentistry & Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: W H
authors.initials: WH
authors.lastname: Lim
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Cheng
authors.forename: B O
authors.initials: BO
authors.lastname: Williams
authors.forename: S J
authors.initials: SJ
authors.lastname: Mah
authors.forename: J A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000473:pathology; D000818:Animals; D060466:Axin Protein / Q000235:genetics; D003238:Connective Tissue / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D003739:Dental Cementum / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D000071235:Fibromodulin; D006706:Homeostasis / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009804:Odontoblasts / Q000473:pathology; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D053495:Osteopontin / Q000032:analysis; D010513:Periodontal Ligament / Q000473:pathology / Q000502:physiology*; D011509:Proteoglycans / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000076182:Sp7 Transcription Factor; D014092:Tooth Root / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis; D060449:Wnt Signaling Pathway / Q000502:physiology*; D060508:Wnt3 Protein / Q000494:pharmacology; D055114:X-Ray Microtomography / Q000379:methods; D016335:Zinc Fingers; D051176:beta Catenin / Q000032:analysis
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; C495267:CTNNB1 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C493597:Lgr5 protein, mouse; D011509:Proteoglycans; D043562:Receptors, G-Protein-Coupled; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C506896:Spp1 protein, mouse; D014157:Transcription Factors; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D051176:beta Catenin; D015675:Osteocalcin; D053495:Osteopontin; D000071235:Fibromodulin; D000469:Alkaline Phosphatase
keywords: Wntless; osteogenic factor; periodontal ligament; width