Dentin Sialophosphoprotein Is Processed by MMP-2 and MMP-20 in Vitro and in Vivo

Yamakoshi, Yasuo; Hu, Jan C.‐C.; Iwata, Takanori; Kobayashi, Kazuyuki; Fukae, Makoto; Simmer, James P.

doi:10.1074/jbc.m607767200

Cited by 116 publications

(140 citation statements)

References 41 publications

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“…Along these lines, the molecular redundancy of MMP2 and MMP20 in cleaving DSPP [33] may have permitted pseudogenization of MMP20 once it was released from performing its unique function in enamel formation.…”

Section: Resultsmentioning

confidence: 99%

Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales

et al. 2010

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Whales in the suborder Mysticeti are filter feeders that use baleen to sift zooplankton and small fish from ocean waters. Adult mysticetes lack teeth, although tooth buds are present in foetal stages. Cladistic analyses suggest that functional teeth were lost in the common ancestor of crown-group Mysticeti. DNA sequences for the tooth-specific genes, ameloblastin (AMBN), enamelin (ENAM) and amelogenin (AMEL), have frameshift mutations and/or stop codons in this taxon, but none of these molecular cavities are shared by all extant mysticetes. Here, we provide the first evidence for pseudogenization of a tooth gene, enamelysin (MMP20), in the common ancestor of living baleen whales. Specifically, pseudogenization resulted from the insertion of a CHR-2 SINE retroposon in exon 2 of MMP20. Genomic and palaeontological data now provide congruent support for the loss of enamel-capped teeth on the common ancestral branch of crown-group mysticetes. The new data for MMP20 also document a polymorphic stop codon in exon 2 of the pygmy sperm whale (Kogia breviceps), which has enamel-less teeth. These results, in conjunction with the evidence for pseudogenization of MMP20 in Hoffmann's two-toed sloth (Choloepus hoffmanni), another enamel-less species, support the hypothesis that the only unique, non-overlapping function of the MMP20 gene is in enamel formation.

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Section: Resultsmentioning

confidence: 99%

Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales

et al. 2010

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“…Several proteolytic activities are present in the predentin and dentin 1,19) , including kallikrein 4 (Klk4), matrix metalloproteinase 2(Mmp-2), Mmp-9, a disintegrin and metalloproteinase with thrombospondin motifs 4 (Adamts4), and Mmp-20 [20][21][22][23][24] . These activated proteinases degrade the coexisting proteoglycans following the addition of calcium in vitro 2) .…”

Section: Discussionmentioning

confidence: 99%

A Large Chondroitin Sulfate Proteoglycan, Versican, in Porcine Predentin

Okahata

Yamamoto

Yamakoshi

et al. 2011

Journal of Oral Biosciences

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Proteoglycans and their constituent glycosaminoglycan (GAG) have been proposed to be involved in the inhibition of mineralization in unmineralized tissue, predentin. Among the proteoglycans secreted by odontoblasts, we focused on the large chondroitin sulfate proteoglycan, versican, for its large binding capacity for calcium ions. The aims of this study were the determination of the full-length sequence and splicing variants of the porcine versican, and the detection of versican in the porcine predentin. The complete coding sequence of the porcine versican mRNA was cloned to be 11,775 nucleotides long and encode 3,924 amino acids, and four splicing variants, V0, V1, V2 and V3, were characterized in the isolated porcine cartilage cells. The number of potential GAG attachment sites was 15 in the V0 variant, 13 in the V1 variant, 2 in the V2 variant and 0 in the V3 variant. They were deposited in DDBJ. The V1 variant was determined by RT-PCR in the odontoblasts, dental papilla cells, dental follicle cells, periodontal ligament cells, dental pulp cells, and gingival cells of pigs, although a small amount of the V0 valiant was found in the dental papilla cells. The predentin was prepared from developing porcine permanent incisor tooth germs and its soluble proteins were extracted in order to be partially characterized by protein and proteinase profiles. The versican V1 cleavage products were detected in the predentin extract by Western blotting analysis. These results suggested that the versican splice variant V1 implicates both the control of the mineralization and the activities of the predentin metalloproteinases, because it has 13 GAG chains that bind a large amount of calcium.

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“…We expressed recombinant porcine DSP in bacteria as a GST fusion product and raised polyclonal antibodies that allowed us to isolate DSP from developing pig teeth 25) . Using this antibody we are able to track DSP and DSP-derived cleavage products throughout our purification procedures25- 27) .…”

Section: Dentin Sialoprotein (Dsp)mentioning

confidence: 99%

“…Although the main DGP protein has 81 amino acids, recently we identified several larger versions of the protein ("extended DGPs") that are generated by cleavage of DSP-DGP at alternative sites. The N-terminal sequence of a 22-kDa band has 105 amino acids (Val 368 -Gly 472 ) and is 24 amino acids longer than DGP 27) .…”

Section: Dentin Glycoprotein (Dgp)mentioning

confidence: 99%

“…Very rapidly following its synthesis, DSPP is cleaved by an unidentified protease after Gly 472 , into DSP-DGP (Ile 16 to Gly 472 ) and DPP (Asp 473 to C-terminus). We have successfully isolated these two cleavage products from pig dentin 27) . Even in molars at an early stage of development (before the onset of root formation), a large number of other DSPP pieces are observed in the extracts.…”

Section: Proteolysis Of Dsppmentioning

confidence: 99%

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Dentin Sialophosphoprotein (DSPP) and Dentin

Yamakoshi¹

2008

J. Oral Biosci.

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The revolution in genetics disclosed the types of malformations that occur when expression of a particular gene is lost. In the case of tooth dentin, mutations in the two genes encoding type I collagen cause osteogenesis imperfecta, a bone condition that often includes dentin malformations. Besides collagen, there are a number of non-collagenous proteins in dentin. Among the genes encoding the dentin non-collagenous proteins, only mutations in DSPP (dentin sialophosphoprotein) cause inherited dental malformations. DSPP mutations cause dentinogenesis imperfecta types II and III, and dentin dysplasia type II. DSPP is the most abundant non-collagenous protein in dentin. DSPP protein is necessary for proper dentin formation, and understanding its structure and function should yield important insights into how dentin forms and biomineralization is controlled. DSPP is expressed and secreted by odontoblasts, the cells that make tooth dentin and that also maintain cell processes extending into the mineralized tissue. Following its secretion, DSPP is cleaved into smaller pieces by multiple extracellular proteases. For the last five years I have devoted myself to characterizing DSPP-derived proteins. DSPP is cleaved by proteases into three main parts : dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). We have learned that DSP is a proteoglycan that forms covalent dimers, DGP is a phosphorylated glycoprotein, and DPP is a highly phosphorylated intrinsically disordered protein that shows extensive length polymorphisms due to the genetic heterogeneity of its coding region.

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Dentin Sialophosphoprotein Is Processed by MMP-2 and MMP-20 in Vitro and in Vivo

Cited by 116 publications

References 41 publications

Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales

Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales

A Large Chondroitin Sulfate Proteoglycan, Versican, in Porcine Predentin

Dentin Sialophosphoprotein (DSPP) and Dentin

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