Involvement of matrix metalloproteinases in the onset of dentin mineralization.
In order to study the involvement of matrix metalloproteinases (MMPs) on dentin formation and mineralization, day 18 embryonic mouse tooth germs were cultured for 10 d in the presence or absence of Marimastat, a general MMP inhibitor, or CT(1166), a more selective inhibitor of gelatinases (MMP-2 and MMP-9) and stromelysin-1 (MMP-3). With Marimastat a dose-dependent increase in thickness of the predentin layer and a decreased mineralization of dentin were observed. At the highest concentration of the inhibitor used, enamel formation had ceased. With CT(1166), these effects were already apparent at the lowest concentration used. Western blot analyses demonstrated that the two inhibitors inhibited the expression of enamelysin (MMP-20). These observations indicate that MMPs (possibly MMP-2, -3, -9 and/or -20) play a role in the onset of dentin mineralization. The lack of enamel formation was possibly due to diffusion of amelogenin from its normal site of apposition. The protein clearly was not retained at the surface of the non-mineralized dentin layer, and immunopositive amelogenin accumulated in the odontoblast compartment. The diffusion of enamel proteins and the accumulation revealed by immunolabeling of two small leucine-rich proteoglycans, decorin and biglycan, in the predentin may have contributed to impaired dentin mineralization.
Fanchon
Stephanie
S
Groupe Matrice Extracellulaire et Biominéralizations (EA 2496). Faculté de Chirurgie Dentaire, Université Paris V, Montrouge, France.
Bourd
Katia
K
Septier
Dominique
D
Everts
Vincent
V
Beertsen
Wouter
W
Menashi
Suzanne
S
Goldberg
Michel
M
D053523:Amelogenin; D000577:Amides / Q000494:pharmacology; D000818:Animals; D058578:Biglycan; D046508:Culture Techniques; D058575:Decorin; D003743:Dental Enamel / Q000187:drug effects; D003746:Dental Enamel Proteins / Q000187:drug effects; D003804:Dentin / Q000187:drug effects / Q000502:physiology*; D003810:Dentinogenesis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D053519:Matrix Metalloproteinase 20; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D011509:Proteoglycans / Q000187:drug effects; D014074:Tooth Calcification / Q000187:drug effects / Q000502:physiology*; D014083:Tooth Germ / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
D053523:Amelogenin; C507200:Amelx protein, mouse; D000577:Amides; C546885:Bgn protein, mouse; D058578:Biglycan; C093640:CT 1166; C546879:Dcn protein, mouse; D058575:Decorin; D003746:Dental Enamel Proteins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D009025:Morpholines; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C100342:marimastat; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases; C507113:Mmp20 protein, mouse