title: Genetic evidence for key roles of decorin and biglycan in dentin mineralization.
abstract: Targeted disruption of the dentin sialophosphoprotein (DSPP) gene in the mice (Dspp(-/-)) results in dentin mineralization defects with enlarged predentin phenotype similar to human dentinogenesis imperfecta type III. Using DSPP/biglycan (Dspp(-/-)Bgn(-/0)) and DSPP/decorin (Dspp(-/-)Dcn(-/-)) double knockout mice, here we determined that the enlarged predentin layer in Dspp(-/-) teeth is rescued in the absence of decorin, but not in the absence of biglycan. However, Fourier transform infrared (FTIR) spectroscopy analysis reveals similar hypomineralization of dentin in both Dspp(-/-)Bgn(-/0) and Dspp(-/-)Dcn(-/-) teeth. Atomic force microscopy (AFM) analysis of collagen fibrils in dentin shows subtle differences in the collagen fibril morphology in these genotypes. The reduction of enlarged predentin in Dspp(-/-)Dcn(-/-) mice suggests that the elevated level of decorin in Dspp(-/-) predentin interferes with the mineralization process at the dentin mineralization front. On the other hand, the lack of DSPP and biglycan leads to the increased number of calcospherites in Dspp(-/-)Bgn(-/0) predentin, suggesting that a failure in coalescence of calcospherites was augmented in Dspp(-/-)Bgn(-/0) teeth as compared to Dspp(-/-) teeth. These findings indicate that normal expression of small leucine rich proteoglycans, such as biglycan and decorin, plays an important role in the highly orchestrated process of dentin mineralization.
authors.affiliation: Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Naoto
authors.initials: N
authors.lastname: Haruyama
authors.forename: Taduru L
authors.initials: TL
authors.lastname: Sreenath
authors.forename: Shigeki
authors.initials: S
authors.lastname: Suzuki
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Cherlita
authors.initials: C
authors.lastname: Honeycutt
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.forename: Marian F
authors.initials: MF
authors.lastname: Young
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D058578:Biglycan; D003094:Collagen / Q000648:ultrastructure; D058575:Decorin; D003804:Dentin / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D003811:Dentinogenesis Imperfecta / Q000235:genetics / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007180:Incisor / Q000000981:diagnostic imaging / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008852:Microradiography; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D009804:Odontoblasts / Q000378:metabolism; D010750:Phosphoproteins; D011498:Protein Precursors / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D012795:Sialoglycoproteins; D017550:Spectroscopy, Fourier Transform Infrared; D014074:Tooth Calcification / Q000235:genetics*; D000099311:Dentin Sialophosphoprotein
chemical_list: D058578:Biglycan; D003094:Collagen; D058575:Decorin; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011498:Protein Precursors; D011509:Proteoglycans; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C546884:BGN protein, human; C546885:Bgn protein, mouse; C546878:DCN protein, human; C546879:Dcn protein, mouse