title: Alveolar bone turnover and periodontal ligament width are controlled by Wnt.
abstract: BACKGROUND
  The molecular signals responsible for maintaining homeostatic control over the periodontal ligament (PDL) are unknown. The purpose of this study is to investigate the role of Wnt signaling in this process using gain- and loss-of-function approaches.
  
  
  METHODS
  The function of endogenous Wnt signal in the PDL was evaluated in Lrp5(ACT) mice in which a mutation in the low-density lipoprotein receptor-related protein 5 Wnt coreceptor causes constitutive activation of Wnt signaling, and in adenovirus Dkk1-treated mice in which overexpression of the Wnt inhibitor Dkk1 causes transient Wnt signal inhibition. PDL in both animal models was examined using histology and immunohistochemical analyses for osteopontin, runt-related transcription factor 2 (Runx2), fibromodulin, osterix, ki67, receptor activator of nuclear factor-κB ligand (RANKL), and alkaline phosphatase activity.
  
  
  RESULTS
  Lrp5(ACT) mice exhibited a significant narrowing of the PDL space caused by an increase in osteogenic gene expression, a reduction in RANKL expression and osteoclast activity, and an increase in alveolar bone formation. Conversely, adenovirus Dkk1-treated mice showed decreased expression of osteogenic markers, coupled with an increase in osteoclast activity, which resulted in a slight increase in PDL width.
  
  
  CONCLUSIONS
  The Wnt pathway is involved in the homeostatic control of the PDL, and conditions that elevate or repress Wnt signaling alter the expression of osteogenic genes within the PDL space, which in turn affects its overall width.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lim
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Su-jung
authors.initials: SJ
authors.lastname: Mah
authors.forename: Xing
authors.initials: X
authors.lastname: Yin
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D000539:Alveolar Process / Q000502:physiology*; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis; D000071235:Fibromodulin; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D053495:Osteopontin / Q000032:analysis; D010513:Periodontal Ligament / Q000033:anatomy & histology*; D011509:Proteoglycans / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D000076182:Sp7 Transcription Factor; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000032:analysis; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C501127:Dkk1 protein, mouse; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; C498355:Mki67 protein, mouse; D011509:Proteoglycans; D053245:RANK Ligand; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; C506896:Spp1 protein, mouse; C505689:Tnfsf11 protein, mouse; D014157:Transcription Factors; D053495:Osteopontin; D000071235:Fibromodulin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Bone and bones; cell biology; collagen; gene expression; histology; molecular biology