title: EMMPRIN/CD147 deficiency disturbs ameloblast-odontoblast cross-talk and delays enamel mineralization.
abstract: Tooth development is regulated by a series of reciprocal inductive signaling between the dental epithelium and mesenchyme, which culminates with the formation of dentin and enamel. EMMPRIN/CD147 is an Extracellular Matrix MetalloPRoteinase (MMP) INducer that mediates epithelial-mesenchymal interactions in cancer and other pathological processes and is expressed in developing teeth. Here we used EMMPRIN knockout (KO) mice to determine the functional role of EMMPRIN on dental tissue formation. We report a delay in enamel deposition and formation that is clearly distinguishable in the growing incisor and associated with a significant reduction of MMP-3 and MMP-20 expression in tooth germs of KO mice. Insufficient basement membrane degradation is evidenced by a persistent laminin immunostaining, resulting in a delay of both odontoblast and ameloblast differentiation. Consequently, enamel volume and thickness are decreased in adult mutant teeth but enamel maturation and tooth morphology are normal, as shown by micro-computed tomographic (micro-CT), nanoindentation, and scanning electron microscope analyses. In addition, the dentino-enamel junction appears as a rough calcified layer of approximately 10±5μm thick (mean±SD) in both molars and growing incisors of KO adult mice. These results indicate that EMMPRIN is involved in the epithelial-mesenchymal cross-talk during tooth development by regulating the expression of MMPs. The mild tooth phenotype observed in EMMPRIN KO mice suggests that the direct effect of EMMPRIN may be limited to a short time window, comprised between basement membrane degradation allowing direct cell contact and calcified matrix deposition.
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France.
authors: Mayssam
authors: M
authors: Khaddam
authors: Laboratoire CRRET, Université Paris-Est, CNRS, Créteil, France.
authors: Eric
authors: E
authors: Huet
authors: Laboratoire CRRET, Université Paris-Est, CNRS, Créteil, France.
authors: Benoît
authors: B
authors: Vallée
authors: Laboratoire de Bioingénierie et Biomécanique Ostéo-Articulaire UMR CNRS 7052, Faculté de médecine Lariboisière St. Louis Université Paris 7 Sorbonne Paris Cité, France.
authors: Morad
authors: M
authors: Bensidhoum
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France.
authors: Dominique
authors: D
authors: Le Denmat
authors: Department of Orofacial Development and Regeneration, Institute of Oral Biology, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors: Anna
authors: A
authors: Filatova
authors: Department of Orofacial Development and Regeneration, Institute of Oral Biology, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors: Lucia
authors: L
authors: Jimenez-Rojo
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France.
authors: Sandy
authors: S
authors: Ribes
authors: Fraunhofer Institute for Mechanics of Materials IWM, Walter-Hülse-Str. Halle, Saale, Germany.
authors: Georg
authors: G
authors: Lorenz
authors: Fraunhofer Institute for Mechanics of Materials IWM, Walter-Hülse-Str. Halle, Saale, Germany.
authors: Maria
authors: M
authors: Morawietz
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France.
authors: Gael Y
authors: GY
authors: Rochefort
authors: Fraunhofer Institute for Mechanics of Materials IWM, Walter-Hülse-Str. Halle, Saale, Germany.
authors: Andreas
authors: A
authors: Kiesow
authors: Department of Orofacial Development and Regeneration, Institute of Oral Biology, Center of Dental Medicine, Faculty of Medicine, University of Zurich, Switzerland.
authors: Thimios A
authors: TA
authors: Mitsiadis
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France.
authors: Anne
authors: A
authors: Poliard
authors: Fraunhofer Institute for Mechanics of Materials IWM, Walter-Hülse-Str. Halle, Saale, Germany.
authors: Matthias
authors: M
authors: Petzold
authors: Fondation ophtalmologique A de Rothschild, Université Paris Diderot, PRES Sorbonne Paris Cité, France.
authors: Eric E
authors: EE
authors: Gabison
authors: Laboratoire CRRET, Université Paris-Est, CNRS, Créteil, France.
authors: Suzanne
authors: S
authors: Menashi
authors: EA 2496, Pathologies, Imaging, and Biotherapies of the Tooth, Dental School Université Paris Descartes Sorbonne Paris Cité, France; AP-HP, Odontology Department, Groupement Hospitalier Nord Val de Seine (Bretonneau), France.
authors: Catherine
authors: C
authors: Chaussain
mesh_terms: D000565:Ameloblasts / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D051926:Basigin / Q000378:metabolism*; D003743:Dental Enamel / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003746:Dental Enamel Proteins / Q000378:metabolism; D003804:Dentin / Q000378:metabolism; D007180:Incisor / Q000201:enzymology / Q000254:growth & development; D008334:Mandible / Q000473:pathology / Q000648:ultrastructure; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D008963:Molar / Q000378:metabolism; D009804:Odontoblasts / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D014074:Tooth Calcification; D014083:Tooth Germ / Q000000981:diagnostic imaging / Q000201:enzymology; D055114:X-Ray Microtomography
chemical_list: C497887:Bsg protein, mouse; D003746:Dental Enamel Proteins; D034741:RNA, Small Interfering; C109069:enamel matrix proteins; D051926:Basigin; D020782:Matrix Metalloproteinases
keywords: Cell interaction; Enamel proteins; MMPs; Tooth formation