title: Activation of the Wnt/β-catenin pathway and tissue inhibitor of metalloprotease 1 during tertiary dentinogenesis.
abstract: Tertiary dentin is deposited inside teeth after various stimuli and serves as a major defensive wall to preserve pulp cells. However, the molecular mechanisms of the activation of quiescent odontoblasts, immature pulp cells and tertiary dentin formation are still unclear. Therefore, we performed a comprehensive gene expression analysis of pulp cells after cavity preparation of 9-week-old rat molars to clarify the critical molecules in tertiary dentinogenesis. As a result, mRNA expression of various molecules was up- or down-regulated. Notably, several members of the matrix metalloprotease family and their endogenous inhibitors were up-regulated after cavity preparation. In situ hybridization showed that tissue inhibitor of metalloprotease 1 (Timp1) was widely and continuously distributed in the pulp beneath the cavity in vivo. We also observed accumulation of β-catenin in the pulp cells beneath the cavity by fluorescence immunohistochemistry. Furthermore, Timp1 transcription was repressed by a dominant-negative TCF4 in immature undifferentiated mesenchymal cells, but not altered in mature odontoblast-like cells. These results indicate that cavity preparation may activate the Wnt/β-catenin pathway and the Wnt/β-catenin pathway and Timp1 may be correlatively involved in pulp repair. Timp1 might play crucial roles in reactivation of immature pulp cells for tertiary dentinogenesis.
authors.affiliation: Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Abe
authors.forename: Ikumi
authors.initials: I
authors.lastname: Michikami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imazato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wakisaka
authors.forename: Mikako
authors.initials: M
authors.lastname: Hayashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ebisu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003731:Dental Caries / Q000378:metabolism* / Q000473:pathology; D003737:Dental Cavity Preparation; D003782:Dental Pulp / Q000378:metabolism* / Q000473:pathology; D003804:Dentin / Q000254:growth & development* / Q000473:pathology; D003810:Dentinogenesis; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008963:Molar / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D009804:Odontoblasts / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: C495268:Ctnnb1 protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D051176:beta Catenin