IADR Abstract Archives
Altered Dentinogenesis In Mice Lacking Matrix Metalloproteinase 20 (MMP20)
Objectives: Matrix metalloproteinase 20 (MMP20), a protease produced by ameloblasts, is thought to cleave enamel proteins and participate in other aspects of ameloblast functions. Inactivating mutations in MMP20 cause a recessive form of amelogenesis imperfecta (AI) characterized by hypomineralized, easily fractured enamel. Though Mmp20 mRNA expression has been reported in odontoblasts, its role in dentinogenesis remains to be established. We hypothesized that MMP20 has an important function in dentin formation.
Methods: Mandibles from wild-type (WT) and Mmp20 knock-out (Mmp20-/-) mice (n=4-6) at 30 and 60 days post-natal (dpn) were analyzed by radiography, quantitative micro-computed tomography (micro-CT), histology, and in situ hybridization.
Results: Mmp20 mRNA was highly expressed by odontoblasts during crown and root dentin formation. As anticipated, enamel formation was severely affected and total tooth volume was significantly reduced in Mmp20-/- vs. WT molars at 30 and 60 dpn. Pulp volume was significantly increased by 20% (p<0.0001) in Mmp20-/- vs. WT molars at 30 dpn, though normalized by 60 dpn. Crown and root dentin were analyzed separately to discriminate between direct effects on dentin vs. indirect effects potentially stemming from enamel defects present only in the crown. Crown dentin exhibited 10-20% decreased thickness (p<0.01-0.001) in Mmp20-/- vs. WT molars at both 30 and 60 dpn, and reduced density of 5% (p<0.01) in Mmp20-/- vs. WT molars at 30 dpn, with no significant differences at 60 dpn. Mmp20-/- root dentin also showed reduced dentin thickness (30%; p<0.0001) and mineral density (5%; p<0.05) compared to WT at 30 dpn, however no significant differences were found at 60 dpn.
Conclusions: Genetic ablation of Mmp20 in mice significantly affected both crown and the root dentin. Studies are underway to better understand mechanisms involved and may provide insights into disease processes in AI.
Methods: Mandibles from wild-type (WT) and Mmp20 knock-out (Mmp20-/-) mice (n=4-6) at 30 and 60 days post-natal (dpn) were analyzed by radiography, quantitative micro-computed tomography (micro-CT), histology, and in situ hybridization.
Results: Mmp20 mRNA was highly expressed by odontoblasts during crown and root dentin formation. As anticipated, enamel formation was severely affected and total tooth volume was significantly reduced in Mmp20-/- vs. WT molars at 30 and 60 dpn. Pulp volume was significantly increased by 20% (p<0.0001) in Mmp20-/- vs. WT molars at 30 dpn, though normalized by 60 dpn. Crown and root dentin were analyzed separately to discriminate between direct effects on dentin vs. indirect effects potentially stemming from enamel defects present only in the crown. Crown dentin exhibited 10-20% decreased thickness (p<0.01-0.001) in Mmp20-/- vs. WT molars at both 30 and 60 dpn, and reduced density of 5% (p<0.01) in Mmp20-/- vs. WT molars at 30 dpn, with no significant differences at 60 dpn. Mmp20-/- root dentin also showed reduced dentin thickness (30%; p<0.0001) and mineral density (5%; p<0.05) compared to WT at 30 dpn, however no significant differences were found at 60 dpn.
Conclusions: Genetic ablation of Mmp20 in mice significantly affected both crown and the root dentin. Studies are underway to better understand mechanisms involved and may provide insights into disease processes in AI.