Fibromodulin-deficient Mice Display Impaired Collagen Fibrillogenesis in Predentin as well as Altered Dentin Mineralization and Enamel Formation

Michel Goldberg ^1*, Dominique Septier ¹, Åke Oldberg ¹, Marian F. Young ¹ and Laurent G. Ameye ¹

¹ Laboratoire Réparation et Remodelage des Tissus Oro-Faciaux, EA 4296, Groupe Matrices Extracellulaires et Biominéralisations, Faculté de Chirurgie Dentaire, Université Paris V, Montrouge, France (MG,DS); Lund University, Lund, Sweden (AO); National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland (MFY,LGA); and Nestlé Research Center, Lausanne, Switzerland (LGA)

^* To whom correspondence should be addressed. E-mail: mgoldod{at}aol.com.

Submitted on February 13, 2005
Accepted on 16 November 2005

	Abstract

To determine the functions of fibromodulin, a small leucine-rich keratan sulfate proteoglycan in tooth formation, we investigated the distribution of fibromodulin in dental tissues by immunohistochemistry and characterized the dental phenotype of one-day-old fibromodulin-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 fibromodulin deficient mice and wild-type mice. In normal mice and rats, fibromodulin 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 fibromodulin 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. The staining for DSP and OPN was decreased in molars, while DMP1 and BSP were enhanced. In the incisors, the 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. Taken together, these studies indicate that fibromodulin restricts collagen fibrillogenesis in predentin while promoting dentin mineralization and the early stages of formation of enamel.

Key Words: fibromodulin, dentin, enamel, dentin sialoprotein, dentin matrix protein 1, bone sialoprotein, osteopontin, tooth phenotype

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