title: Downregulation of Wnt causes root resorption.
abstract: BACKGROUND
  There are multiple causes of external root resorption, but absent a disease state, it is most often observed when excessive physical force is used during orthodontic treatment. Even without mechanical stimulation, however, root resorption can still occur. The purpose of this study was to test whether Wnt signaling plays a role in pathologic root resorption, by conditionally deleting Wntless (Wls) from odontoblasts and osteoblasts and then evaluating the phenotypic effects on the maintenance of the root surface.
  
  
  METHODS
  Ten (age, 1 month) and 20 (age, 3 months) OCN-Cre;Wls(fl/fl) mice and their wild-type littermates were evaluated using microcomputed tomography, histology, and immunohistochemistry. Phenotypic alterations in the alveolar bone, dentin, and cementum were characterized and quantified.
  
  
  RESULTS
  In a genetic model of reduced Wnt signaling, we found that RANKL expression is upregulated, and osteoprotegerin expression is downregulated. This molecular disruption results in an increase in osteoclast activity, a decrease in osteoblast activity, and extensive, spontaneous root resorption. A genetic strain of mice in which Wnt signaling is elevated exhibits thicker cementum, whereas, even in the perinatal period, OCN-Cre;Wls(fl/fl) mice exhibit thinner cementum.
  
  
  CONCLUSIONS
  Taken together, these data demonstrate that Wnts regulate cementum homeostasis, and that idiopathic cases of root resorption might have as their etiology a reduction in endogenous Wnt signaling.
authors.affiliation: Researcher, Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, Calif; associate professor, Department of Orthodontics, School of Dentistry & Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lim
authors.affiliation: Research associate, Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, Calif.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Researcher, Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, Calif.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Former researcher, Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, Calif.
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Clinical instructor, Department of Orthodontics, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
authors.forename: Su-jung
authors.initials: SJ
authors.lastname: Mah
authors.affiliation: Professor, Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Stanford University, Stanford, Calif. Electronic address: jhelms@stanford.edu.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000367:Age Factors; D000469:Alkaline Phosphatase / Q000032:analysis / Q000235:genetics; D000539:Alveolar Process / Q000473:pathology; D000818:Animals; D060466:Axin Protein / Q000032:analysis / Q000235:genetics; D003739:Dental Cementum / Q000473:pathology; D003804:Dentin / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009804:Odontoblasts / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics; D053245:RANK Ligand / Q000032:analysis / Q000235:genetics; D012391:Root Resorption / Q000235:genetics* / Q000473:pathology; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics; D000071681:Tartrate-Resistant Acid Phosphatase; D019237:Tooth Cervix / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins / Q000032:analysis / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D055114:X-Ray Microtomography; D000099311:Dentin Sialophosphoprotein
chemical_list: D000135:Acid Phosphatase; D000469:Alkaline Phosphatase; D060466:Axin Protein; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D010750:Phosphoproteins; D053245:RANK Ligand; D012795:Sialoglycoproteins; D000071681:Tartrate-Resistant Acid Phosphatase; D051153:Wnt Proteins; D000099311:Dentin Sialophosphoprotein; C111729:Axin2 protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse