International Journal of Oral Biology

  • 제34권1호
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  • Pages.21-28
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  • 2009
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  • 1226-7155(pISSN)
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  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
권호 표지

The Expression of Matrix Metalloprotease 20 is Stimulated by Wild Type but not by 4 bp- or 2 bp-Deletion Mutant DLX3

  • Park, Hyun-Jung (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Ryoo, Hyun-Mo (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Woo, Kyung-Mi (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Kim, Gwan-Shik (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Baek, Jeong-Hwa (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
  • 발행 : 2009.03.31
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초록

Mutations in DLX3 are associated with both autosomal dominant hypoplastic hypomaturation amelogenesis imperfecta (ADHHAI) and tricho-dento-osseous (TDO) syndrome. ADHHAI is caused by a c.561_562delCT (2bp-del DLX3) mutation whereas TDO syndrome is associated with a c.571_574delGGGG (4bp-del DLX3) mutation. However, although the causal relationships between DLX3 and an enamel phenotype have been established, the pathophysiological role of DLX3 mutations in enamel development has not yet been clarified. In our current study, we prepared expression vectors for wild type and deletion mutant DLX3 products (4bp-del DLX3, 2bp-del DLX3) and examined the effects of their overexpression on the expression of the enamel matrix proteins and proteases. Wild type DLX3 enhanced the expression of matrix metalloprotease 20 (MMP20) mRNA and protein in murine ameloblast-like cells. However, neither a 4bp-del nor 2bp-del DLX3 increased MMP20 expression. Wild type DLX3, but not the above DLX3 mutants, also increased the activity of reporters containing 1.5 kb or 0.5 kb of the MMP20 promoter. An examination of protein stability showed that the half-life of wild type DLX3 protein was less than 12 h whilst that of both deletion mutants was longer than 24 h. Endogenous Dlx3 was also found to be continuously expressed during ameloblast differentiation. Since inactivating mutations in the gene encoding MMP20 are associated with amelogenesis imperfecta, the inability of 4bp-del or 2bp-del DLX3 to induce MMP20 expression suggests a possible involvement of such mutations in the enamel phenotype associated with TDO syndrome or ADHHAI.

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참고문헌

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