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Regulation of biomineralization by dentin matrix protein 1
Author(s) -
Qin Chunlin,
Sun Yao
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.185.2
Subject(s) - dmp1 , transgene , genetically modified mouse , chemistry , microbiology and biotechnology , in vivo , biomineralization , dentin , biology , biochemistry , gene , pathology , genetics , medicine , viral matrix protein , paleontology
Dentin matrix protein 1 (DMP1) plays a crucial role in osteogenesis and dentinogenesis. DMP1 in bone and dentin is processed into fragments. To test the hypothesis that DMP1 processing is essential to biomineralization, we generated transgenic mice expressing DMP1, in which Asp213, a residue at a key‐cleavage site, was substituted by Ala213 (D213A‐DMP1). By crossbreeding these transgenic mice with Dmp1 knockout (Dmp1‐KO) mice, we obtained mice (“Dmp1‐KO/D213A‐Tg”) expressing D213A‐DMP1 in Dmp1‐KO background. The skeletal and dental phenotypes of Dmp1‐KO/D213A‐Tg mice were compared to wild type mice, Dmp1‐KO mice and Dmp1‐KO mice expressing the normal Dmp1 transgene. These analyses showed that D213A substitution effectively blocked the proteolytic processing of DMP1 in vivo. While the expression of the normal Dmp1 transgene rescued the skeletal and dental changes of the Dmp1‐KO mice, the expression of D213A‐Dmp1 transgene failed to do so. These results indicate that the full‐length form of DMP1 is an inactive precursor and its proteolytic processing is an activation step, essential to the biological functions of this protein in biomineralization. This work was supported by NIH Grant DE 005092 (to CQ)