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 E xtracellular M atrix M etallo PR oteinase (MMP) IN ducer that mediates epithelial–mesenc...

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Published in:Bone (New York, N.Y.) N.Y.), 2014-09, Vol.66, p.256-266
Main Authors: Khaddam, Mayssam, Huet, Eric, Vallée, Benoît, Bensidhoum, Morad, Le Denmat, Dominique, Filatova, Anna, Jimenez-Rojo, Lucia, Ribes, Sandy, Lorenz, Georg, Morawietz, Maria, Rochefort, Gael Y, Kiesow, Andreas, Mitsiadis, Thimios A, Poliard, Anne, Petzold, Matthias, Gabison, Eric E, Menashi, Suzanne, Chaussain, Catherine
Format: Article
Language:English
Subjects:
Ameloblasts - metabolism
Ameloblasts - pathology
Animals
Basement Membrane - metabolism
Basigin - metabolism
Biological and medical sciences
Cell interaction
Cell physiology
Dental Enamel - diagnostic imaging
Dental Enamel - physiopathology
Dental Enamel Proteins - metabolism
Dentin - metabolism
Enamel proteins
Fundamental and applied biological sciences. Psychology
Human health and pathology
Incisor - enzymology
Incisor - growth & development
Life Sciences
Mandible - pathology
Mandible - ultrastructure
Matrix Metalloproteinases - metabolism
Mice, Inbred C57BL
Mice, Knockout
Mineralization, calcification
MMPs
Models, Biological
Molar - metabolism
Molecular and cellular biology
Odontoblasts - metabolism
Odontoblasts - pathology
Orthopedics
Phenotype
RNA, Small Interfering - metabolism
Tissues and Organs
Tooth Calcification
Tooth formation
Tooth Germ - diagnostic imaging
Tooth Germ - enzymology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
X-Ray Microtomography
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Summary: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 E xtracellular M atrix M etallo PR oteinase (MMP) IN ducer 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 ± 5 μm 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.
ISSN:8756-3282
1873-2763
8756-3282
DOI:10.1016/j.bone.2014.06.019