Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization.
Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is proteolytically cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Our previous studies revealed that DSPP null mice display a phenotype similar to human autosomal dominant dentinogenesis imperfecta, in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Earlier in vitro studies suggested that DPP, but not DSP, plays a significant role in initiation and maturation of dentin mineralization. However, the precise in vivo roles of DSP and DPP are far from clear. Here we report the generation of DPPcKO mice, in which only DSP is expressed in a DSPP null background, resulting in a conditional DPP knockout. DPPcKO teeth show a partial rescue of the DSPP null phenotype with the restored predentin width, an absence of irregular unmineralized areas in dentin, and less frequent pulp exposure. Micro-computed tomography (micro-CT) analysis of DPPcKO molars further confirmed this partial rescue with a significant recovery in the dentin volume, but not in the dentin mineral density. These results indicate distinct roles of DSP and DPP in dentin mineralization, with DSP regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin.
Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health/DHHS, 30 Convent Drive, Bethesda, MD 20892, USA.
Shigeki
S
Suzuki
Taduru
T
Sreenath
Naoto
N
Haruyama
Cherlita
C
Honeycutt
Anita
A
Terse
Andrew
A
Cho
Thomas
T
Kohler
Ralph
R
Müller
Michel
M
Goldberg
Ashok B
AB
Kulkarni
D000818:Animals; D002809:Chondroitin Sulfates / Q000378:metabolism; D003789:Dental Pulp Exposure / Q000235:genetics / Q000473:pathology; D003804:Dentin / Q000378:metabolism*; D003810:Dentinogenesis / Q000235:genetics / Q000502:physiology*; D003871:Dermatan Sulfate / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental; D005813:Genes, Synthetic; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008903:Minerals / Q000378:metabolism; D008963:Molar / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D016326:Extracellular Matrix Proteins; D008903:Minerals; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein