title: Morphogenetic roles of perlecan in the tooth enamel organ: an analysis of overexpression using transgenic mice.
abstract: Perlecan, a heparan sulfate proteoglycan, is enriched in the intercellular space of the enamel organ. To understand the role of perlecan in tooth morphogenesis, we used a keratin 5 promoter to generate transgenic (Tg) mice that over-express perlecan in epithelial cells, and examined their tooth germs at tissue and cellular levels. Immunohistochemistry showed that perlecan was more strongly expressed in the enamel organ cells of Tg mice than in wild-type mice. Histopathology showed wider intercellular spaces in the stellate reticulum of the Tg molars and loss of cellular polarity in the enamel organ, especially in its cervical region. Hertwig's epithelial root sheath (HERS) cells in Tg mice were irregularly aligned due to excessive deposits of perlecan along the inner, as well as on the outer sides of the HERS. Tg molars had dull-ended crowns and outward-curved tooth roots and their enamel was poorly crystallized, resulting in pronounced attrition of molar cusp areas. In Tg mice, expression of integrin β1 mRNA was remarkably higher at E18, while expression of bFGF, TGF-β1, DSPP and Shh was more elevated at P1. The overexpression of perlecan in the enamel organ resulted in irregular morphology of teeth, suggesting that the expression of perlecan regulates growth factor signaling in a stage-dependent manner during each step of the interaction between ameloblast-lineage cells and mesenchymal cells.
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Satokata
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sato
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D003743:Dental Enamel / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D004658:Enamel Organ / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007178:Inbreeding; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009805:Odontogenesis; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014070:Tooth / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D019228:Tooth Crown / Q000378:metabolism; D014092:Tooth Root / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D055114:X-Ray Microtomography
chemical_list: D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; D019012:Integrin beta1; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D012333:RNA, Messenger; C465570:Shh protein, mouse; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C071927:perlecan