title: Fibromodulin-deficient mice display impaired collagen fibrillogenesis in predentin as well as altered dentin mineralization and enamel formation.
abstract: To determine the functions of fibromodulin (Fmod), a small leucine-rich keratan sulfate proteoglycan in tooth formation, we investigated the distribution of Fmod in dental tissues by immunohistochemistry and characterized the dental phenotype of 1-day-old Fmod-deficient mice using light and transmission electron microscopy. Immunohistochemistry was also used to compare the relative protein expression of dentin sialoprotein (DSP), dentin matrix protein-1 (DMP 1), bone sialoprotein (BSP), and osteopontin (OPN) between Fmod-deficient mice and wild-type mice. In normal mice and rats, Fmod immunostaining was mostly detected in the distal cell bodies of odontoblasts and in the stratum intermedium and was weaker in odontoblast processes and predentin. The absence of Fmod impaired dentin mineralization, increased the diameter of the collagen fibrils throughout the whole predentin, and delayed enamel formation. Immunohistochemistry provides evidence for compensatory mechanisms in Fmod-deficient mice. Staining for DSP and OPN was decreased in molars, whereas DMP 1 and BSP were enhanced. In the incisors, labeling for DSP, DMP 1, and BSP was strongly increased in the pulp and odontoblasts, whereas OPN staining was decreased. Positive staining was also seen for DMP 1 and BSP in secretory ameloblasts. Together these studies indicate that Fmod restricts collagen fibrillogenesis in predentin while promoting dentin mineralization and the early stages of enamel formation.
authors.affiliation: Laboratoire Réparation et Remodelage des Tissus Oro-Faciaux, EA 4296, Groupe Matrices extracellulaires et biominéralisations, Faculté de Chirurgie Dentaire, Université Paris V, Montrouge, France. mgoldod@aol.com
authors.forename: Michel
authors.initials: M
authors.lastname: Goldberg
authors.forename: Dominique
authors.initials: D
authors.lastname: Septier
authors.forename: Ake
authors.initials: A
authors.lastname: Oldberg
authors.forename: Marian F
authors.initials: MF
authors.lastname: Young
authors.forename: Laurent G
authors.initials: LG
authors.lastname: Ameye
mesh_terms: D053523:Amelogenin; D000818:Animals; D000831:Animals, Newborn; D003743:Dental Enamel / Q000254:growth & development / Q000502:physiology*; D003746:Dental Enamel Proteins / Q000096:biosynthesis; D003804:Dentin / Q000000981:diagnostic imaging / Q000254:growth & development / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D024022:Fibrillar Collagens / Q000502:physiology*; D000071235:Fibromodulin; D007150:Immunohistochemistry; D007180:Incisor / Q000254:growth & development / Q000378:metabolism; D058574:Integrin-Binding Sialoprotein; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D008963:Molar / Q000254:growth & development / Q000378:metabolism; D053495:Osteopontin; D010750:Phosphoproteins / Q000096:biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D051381:Rats; D012795:Sialoglycoproteins / Q000096:biosynthesis; D014074:Tooth Calcification; D014463:Ultrasonography; D000099311:Dentin Sialophosphoprotein
chemical_list: D053523:Amelogenin; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; D000071235:Fibromodulin; D058574:Integrin-Binding Sialoprotein; D053495:Osteopontin; D010750:Phosphoproteins; D011498:Protein Precursors; D011509:Proteoglycans; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C507200:Amelx protein, mouse; C507201:Amelx protein, rat; C513308:Dmp1 protein, mouse; C081635:Dmp1 protein, rat; C000604332:Fmod protein, mouse; C000604334:Fmod protein, rat; C546872:Ibsp protein, mouse; C546873:Ibsp protein, rat; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat