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Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III.
J Biol Chem. 2003 Jul 04; 278(27):24874-80.JB

Abstract

Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.

Authors+Show Affiliations

Functional Genomics Unit and Gene Targeting Facility, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. tsreenat@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12721295

Citation

Sreenath, Taduru, et al. "Dentin Sialophosphoprotein Knockout Mouse Teeth Display Widened Predentin Zone and Develop Defective Dentin Mineralization Similar to Human Dentinogenesis Imperfecta Type III." The Journal of Biological Chemistry, vol. 278, no. 27, 2003, pp. 24874-80.
Sreenath T, Thyagarajan T, Hall B, et al. Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III. J Biol Chem. 2003;278(27):24874-80.
Sreenath, T., Thyagarajan, T., Hall, B., Longenecker, G., D'Souza, R., Hong, S., Wright, J. T., MacDougall, M., Sauk, J., & Kulkarni, A. B. (2003). Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III. The Journal of Biological Chemistry, 278(27), 24874-80.
Sreenath T, et al. Dentin Sialophosphoprotein Knockout Mouse Teeth Display Widened Predentin Zone and Develop Defective Dentin Mineralization Similar to Human Dentinogenesis Imperfecta Type III. J Biol Chem. 2003 Jul 4;278(27):24874-80. PubMed PMID: 12721295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III. AU - Sreenath,Taduru, AU - Thyagarajan,Tamizchelvi, AU - Hall,Bradford, AU - Longenecker,Glenn, AU - D'Souza,Rena, AU - Hong,Sung, AU - Wright,J Tim, AU - MacDougall,Mary, AU - Sauk,John, AU - Kulkarni,Ashok B, Y1 - 2003/04/29/ PY - 2003/5/2/pubmed PY - 2003/8/19/medline PY - 2003/5/2/entrez SP - 24874 EP - 80 JF - The Journal of biological chemistry JO - J Biol Chem VL - 278 IS - 27 N2 - Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12721295/Dentin_sialophosphoprotein_knockout_mouse_teeth_display_widened_predentin_zone_and_develop_defective_dentin_mineralization_similar_to_human_dentinogenesis_imperfecta_type_III_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)86947-6 DB - PRIME DP - Unbound Medicine ER -