Matrix metalloproteinase inhibition impairs the processing, formation and mineralization of dental tissues during mouse molar development.
Organotypic cultures of embryonic mouse tooth germs were used to investigate the developmental expression and roles of MMPs in the formation and mineralization of dentin and enamel matrices. The spatially and temporally regulated expression of MMP-2, MMP-9 and MMP-20 in developing mouse tooth germs in vivo was maintained in culture. The inhibition of metalloproteinases activity by marimastat altered the morphogenesis and mineralization of the tooth germs associated with an inhibition of the activation of both MMP-20 and MMP-2. MMP inhibition deregulated the molecular processing of two major dental matrix proteins, amelogenin and dentin sialoprotein (DSP). This coincided with their accumulation and the loss of their normal distribution within the extracellular matrix, resulting in a defective mineralization of dentin and enamel matrices. These findings demonstrate the critical role of MMPs in the processing and maturation of the dental matrix.
Bourd-Boittin
Katia
K
Matrices Extracellulaires et Biominéralisation, EA 2496, Faculté de Chirurgie Dentaire, Université René Descartes Paris V, Montrouge, France.
Fridman
Rafael
R
Fanchon
Stéphanie
S
Septier
Dominique
D
Goldberg
Michel
M
Menashi
Suzanne
S
D000566:Amelogenesis / Q000502:physiology; D053523:Amelogenin; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D003743:Dental Enamel / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000378:metabolism; D003804:Dentin / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D003810:Dentinogenesis / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005260:Female; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053519:Matrix Metalloproteinase 20; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008963:Molar / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D009805:Odontogenesis / Q000502:physiology*; D009924:Organ Culture Techniques; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
D053523:Amelogenin; D003746:Dental Enamel Proteins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D006877:Hydroxamic Acids; D020778:Matrix Metalloproteinase 2; D053519:Matrix Metalloproteinase 20; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C507200:Amelx protein, mouse; C100342:marimastat; C507113:Mmp20 protein, mouse