title: Accelerated enamel mineralization in Dspp mutant mice.
abstract: Dentin sialophosphoprotein (DSPP) is one of the major non-collagenous proteins present in dentin, cementum and alveolar bone; it is also transiently expressed by ameloblasts. In humans many mutations have been found in DSPP and are associated with two autosomal-dominant genetic diseases - dentinogenesis imperfecta II (DGI-II) and dentin dysplasia (DD). Both disorders result in the development of hypomineralized and mechanically compromised teeth. The erupted mature molars of Dspp(-/-) mice have a severe hypomineralized dentin phenotype. Since dentin and enamel formations are interdependent, we decided to investigate the process of enamel onset mineralization in young Dspp(-/-) animals. We focused our analysis on the constantly erupting mouse incisor, to capture all of the stages of odontogenesis in one tooth, and the unerupted first molars. Using high-resolution microCT, we revealed that the onset of enamel matrix deposition occurs closer to the cervical loop and both secretion and maturation of enamel are accelerated in Dspp(-/-) incisors compared to the Dspp(+/-) control. Importantly, these differences did not translate into major phenotypic differences in mature enamel in terms of the structural organization, mineral density or hardness. The only observable difference was the reduction in thickness of the outer enamel layer, while the total enamel thickness remained unchanged. We also observed a compromised dentin-enamel junction, leading to delamination between the dentin and enamel layers. The odontoblast processes were widened and lacked branching near the DEJ. Finally, for the first time we demonstrate expression of Dspp mRNA in secretory ameloblasts. In summary, our data show that DSPP is important for normal mineralization of both dentin and enamel.
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15261F, United States; Department of Endodontics, School of Dental Medicine, University of Pittsburgh, PA 15261, United States; Mineralized Tissues Laboratory, Hospital for Special Surgery, New York, NY 10021, United States.
authors.forename: Kostas
authors.initials: K
authors.lastname: Verdelis
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15261F, United States; Department of Developmental Biology, School of Medicine, University of Pittsburgh, PA 15201, United States.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Szabo-Rogers
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Chong
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Kang
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cusack
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States.
authors.forename: Priyam
authors.initials: P
authors.lastname: Jani
authors.affiliation: Mineralized Tissues Laboratory, Hospital for Special Surgery, New York, NY 10021, United States.
authors.forename: Adele L
authors.initials: AL
authors.lastname: Boskey
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
authors.affiliation: Center for Craniofacial Regeneration, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, PA 15261, United States; McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15261F, United States; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15216, United States. Electronic address: ebeniash@pitt.edu.
authors.forename: Elia
authors.initials: E
authors.lastname: Beniash
mesh_terms: D000566:Amelogenesis; D000818:Animals; D003743:Dental Enamel / Q000000981:diagnostic imaging*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics*; D017001:Tooth Demineralization / Q000000981:diagnostic imaging* / Q000235:genetics; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
keywords: Dentin; Dentin sialophosphoprotein; Dentino-enamel junction; Enamel; Odontogenesis