title: Wnt signaling regulates pulp volume and dentin thickness.
abstract: Odontoblasts, cementoblasts, ameloblasts, and osteoblasts all form mineralized tissues in the craniofacial complex, and all these cell types exhibit active Wnt signaling during postnatal life. We set out to understand the functions of this Wnt signaling, by evaluating the phenotypes of mice in which the essential Wnt chaperone protein, Wntless was eliminated. The deletion of Wls was restricted to cells expressing Osteocalcin (OCN), which in addition to osteoblasts includes odontoblasts, cementoblasts, and ameloblasts. Dentin, cementum, enamel, and bone all formed in OCN-Cre;Wls(fl/fl) mice but their homeostasis was dramatically affected. The most notable feature was a significant increase in dentin volume and density. We attribute this gain in dentin volume to a Wnt-mediated misregulation of Runx2. Normally, Wnt signaling stimulates Runx2, which in turn inhibits dentin sialoprotein (DSP); this inhibition must be relieved for odontoblasts to differentiate. In OCN-Cre;Wls(fl/fl) mice, Wnt pathway activation is reduced and Runx2 levels decline. The Runx2-mediated repression of DSP is relieved and odontoblast differentiation is accordingly enhanced. This study demonstrates the importance of Wnt signaling in the homeostasis of mineralized tissues of the craniofacial complex.
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: Won Hee
authors.initials: WH
authors.lastname: Lim
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Du
authors.initials: D
authors.lastname: Cheng
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Ramos
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Claire
authors.initials: C
authors.lastname: Bardet
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Mah
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D003782:Dental Pulp / Q000033:anatomy & histology*; D003804:Dentin / Q000033:anatomy & histology*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D051153:Wnt Proteins
keywords: DENTIN; ODONTOBLAST; PULP; WNT SIGNALING PATHWAY