Characterization of Periodontal Structures of Enamelin-Null Mice

• Autores: Chan Hsun-Liang
• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 1, 2014, págs. 195-203
• Idioma: inglés
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• Resumen

  • Background: Enamelin-null (ENAM-/-) mice have no enamel. When characterizing ENAM-/- mice, alveolar bone height reduction was observed, and it was hypothesized that enamel defects combined with diet are associated with the periodontal changes of ENAM-/-mice. The aim of the present study is to compare the dimension of interradicular bone of ENAM-/- (knock-out [KO]) with wild-type (WT) mice, maintained on hard (HC) or soft (SC) chow.

    Methods: A total of 100 animals divided into four groups were studied at 3, 8, and 24 weeks of age: 1) KO/HC; 2) KO/SC; 3) WT/HC; and 4) WT/SC. Microcomputed tomography was performed, and the following measurements were made between mandibular first (M1) and second (M2) molars: relative alveolar bone height (RBH), crestal bone width (CBW), bone volume (BV), bone mineral content (BMC), and bone mineral density (BMD). The position of M1 and M2 in relation to the inferior border of the mandible was also determined at 24 weeks. All variables were analyzed by one-way analysis of variance and Dunnett test for pairwise comparisons. Morphologic analyses were conducted on hematoxylin and eosin�stained sections.

    Results: Radiographically, the enamel layer was absent in ENAM-/- mice. Interproximal open contacts were observed exclusively in ENAM-/- mice, and the prevalence decreased over time, suggesting that a shifting of tooth position had occurred. Additionally, in the two ENAM-/- groups, RBH was significantly lower at 8 and 24 weeks (P <0.02); CBW, BV, and BMC were significantly less (P <0.05) at 24 weeks. No differences in BMD were found among the four groups. The molars migrated to a more coronal position in ENAM-/- mice and mice on HC. Histologic findings were consistent with radiographic observations. After eruption, the junctional epithelium was less organized in ENAM-/- mice.

    Conclusion: The interdental bone density was not affected in the absence of enamelin, but its volume was, which is likely a consequence of alternations in tooth position.

    Enamelin is the largest enamel matrix protein, and its cleavage products cumulate to make up 5% of the enamel matrix. Defects in human enamelin (ENAM, 4q13.2) cause autosomal-dominant amelogenesis imperfecta (AI). To date, 16 ENAM mutations are associated with autosomal-dominant AI.1-16 In general, the clinical features include thin enamel with either severe or localized hypoplasia.6 The enamel phenotype is dose dependent and ranges from small, well-circumscribed enamel pits to enamel agenesis.12 Mutations induced with the mutagen N-ethyl-N-nitrosourea resulted in four separate ENAM point mutations: 1) p.S55I; 2) p.E57G; 3) the splice donor site in exon 4; and 4) p.Q176X.17,18 Heterozygous mice exhibited rough and pitted enamel, whereas the null mice showed enamel agenesis. Enamelin gene knock-out (KO) and LacZ knock-in mice were generated by replacing the ENAM coding sequence from the translation initiation site through exon 7 with a lacZ reporter gene.19 The enamel layer is completely absent in enamelin-null (ENAM-/-) mice compared with the mild enamel phenotype in the heterozygotes (ENAM+/-). A thin, highly irregular, easily abraded mineralized crust over the dentin is observed in ENAM-/- mice. The affected teeth have significant wear and are generally chalky white. The histologic, morphometric, and protein/mineral analyses demonstrate that enamelin is essential for proper enamel matrix organization and mineralization.

    Enamelin, like other enamel matrix proteins, is strictly expressed by ameloblasts during the secretory stage of amelogenesis;19 as a result, it is unlikely that the absence of enamelin will have a direct effect on periodontium. Interestingly, during the assessment of the body weight of Enam-/- mice, it was observed that the level of alveolar bone seemed decreased, which was also influenced by food texture. From the characterization of ENAM-/- mice,20 differences in their periodontia compared with wild-type (WT) mice were noticed. Periodontal changes around the mandibular molars, with appreciable bone loss, widened interdental spaces, and furcation involvement in the first molars (M1) and sometimes second molars (M2) were observed among the ENAM-/- mice. This study is designed to compare the dimension of interradicular bone between mandibular M1 and M2 of ENAM-/- KO and WT mice, maintained on hard (HC) or soft (SC) chow. In addition, assessment was made to determine whether there were additional periodontal changes among the KO mice.