title: The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation.
abstract: Runx2, of the Runx family, is an essential transcription factor that controls bone and tooth development by regulating osteoblast and odontoblast differentiation. However, the function of Runx2 in late stage odontoblast differentiation is not clear. We studied the function of Runx2 in dentinogenesis by generating transgenic mice expressing Runx2 specifically in odontoblasts. We observed dentin formation in postnatal day 3 (P3), P7 and P28 mice and measured the expression levels of Runx2 and matrix proteins in dentin. The odontoblasts in transgenic mice (Tg) lost their tall columnar shape and polarization and dentinal tubules were absent. The dental pulp chamber was dramatically enlarged and the dentin in Tg mice was thinner. Osteoblast-like cells were seen instead of normal odontoblasts and were embedded in a bone-like matrix, indicating that dentin formation was replaced with bone. Predentin was disorganized possessing lacunae that contained odontoblasts. The mandibular molars of Tg mice showed noticeable defects by Micro-CT. Using quantitative real-time PCR, the expression of dentin matrix proteins, particularly dentin sialophosphoprotein (DSPP), was found to be upregulated in 3-day-old Tg mice and downregulated at 1 month of age. These findings indicate that Runx2 inhibited odontoblast terminal differentiation and induced transdifferentiation of odontoblasts to osteoblasts at the late cell differentiation stage. Therefore, Runx2 should be inhibited in odontoblasts to encourage normal cell maturation, differentiation and dentinogenesis.
authors.affiliation: Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Shiting
authors.initials: S
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.forename: Naihui
authors.initials: N
authors.lastname: Yao
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Kuang
authors.forename: Xiu
authors.initials: X
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Zhu
authors.forename: Longxing
authors.initials: L
authors.lastname: Ni
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D003804:Dentin / Q000254:growth & development*; D003810:Dentinogenesis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008963:Molar / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D009804:Odontoblasts / Q000166:cytology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse