Disease relevance of DMP1

• Because all of these proteins were also shown by immunohistochemistry to be expressed in serial sections of a colon adenocarcinoma, we have hypothesized that the MMP-9/DMP1/cell surface complexes observed to enhance cell invasion in vitro may be aiding metastatic events in vivo [1].
• In this study, we used a modified Boyden chamber assay to show that DMP1 enhanced the invasiveness of the MMP-9 expressing colon cancer cell line, SW480, through Matrigel in a dose-dependant manner [1].
• The role of DMP1 in lung cancer is largely unknown [2].
• RESULTS: Our results show that DMP1 is detectable in 90% of the adenocarcinoma and squamous carcinoma analyzed while 8 of 10 bronchioloalveolar specimens were negative [2].
• It was detectable in 80% of the cases, suggesting a potential role for DMP1 in tumor progression and bone metastasis [2].

High impact information on DMP1

• Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype [3].
• Two new reports extend the functions of DMP1, a bone matrix protein involved in mineralization, to phosphate regulation [4].
• Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism [3].
• Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus [3].
• DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis [5].

Chemical compound and disease context of DMP1

• Following acid etching of the dentinal surface with maleic acid/HEMA, the smear layer was removed, and a superficial zone was demineralized in such a way that the exposed collagenous dentin matrix retained its integrity [6].
• The antibacterial activity of chlorhexidine digluconate and iodine potassium iodide on Enterococcus faecalis A197A was tested in the presence of dentin, dentin matrix, dentin pretreated by EDTA and citric acid, collagen, and heat-killed cells of Enterococcus faecalis and Candida albicans [7].
• Inactivation of the antibacterial activity of iodine potassium iodide and chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix, type-I collagen, and heat-killed microbial whole cells [7].

Biological context of DMP1

• In this study, we have used histological and RFLP analyses of tissues from a DGI-II-affected patient, as compared with two normal controls, to determine if DMP1, 2, or 3 was linked to DGI-II [8].
• We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets [9].
• Enforced coexpression of either of three D-type cyclins (D1, D2, or D3) with DMP1 in mammalian cells canceled its ability to activate gene expression [10].
• In the extracellular matrix of these tissues DMP1 is present as fragments representing the NH2-terminal (37 kDa) and COOH-terminal (57 kDa) portions of the cDNA-deduced amino acid sequence [11].
• We purified DMP1-PG with a monoclonal anti-DMP1 antibody affinity column [11].

Anatomical context of DMP1

• Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation [12].
• These distinct extracellular patterns may be related to the nature of DSPP, OC, and ON interactions with other matrix-specific macromolecules (i.e., amelogenin, dentin matrix protein-1) and/or to the polarized organization of odontoblast secretion as compared with osteoblasts [13].
• Introduction of DMP1 into mouse NIH 3T3 fibroblasts inhibited entry into S phase [10].
• A critical cis-regulatory element located between nt -150 and -63 was found to act as a specific silencer responsible for the negative regulation of DMP1 in HepG2 and HeLa cells [14].
• Real-time PCR analyses of ADM and DMP-1 in a panel of healthy and carious pulpal tissue and also in immune system cells highlighted the heterogeneity of caries and indicated increased expression of ADM in neutrophils activated by bacterial products [15].

Associations of DMP1 with chemical compounds

• Our findings show that in addition to its existence as a phosphoprotein, the NH2-terminal fragment from DMP1 occurs as a proteoglycan [11].
• Another member of this family, dentin matrix protein 1, is shown in this paper to be very similar to osteopontin in that it can bind strongly to Factor H (K(a) approximately 1 nm) and block the lytic activity through either the vitronectin receptor (alpha(V)beta(3) integrin) or CD44 [16].
• Both full-length recombinant DMP1 and post-translationally modified native DMP1 were able to nucleate hydroxyapatite (HAP) in the presence of type I collagen [17].
• Collagen matrix impregnated with recombinant DMP1 was implanted directly in Group 1, while calcium hydroxide, a commonly used pulp-capping agent was implanted in group 2, collagen matrix that was not impregnated with rDMP1 was implanted directly in group 3, which served as control [18].
• The translated proto- and metatherian protein sequences are highly divergent from the eutherian sequences but retain the general characteristics of the DMP1 (high acidity, serine-richness, multiple glycosylation sites, and the presence of the RGD cell attachment tripeptide) [19].
• Expression of alphaVbeta3 integrin enhanced HSG attachment to DMP1 and OPN and promoted haptotactic migration onto all three proteins [20].

Physical interactions of DMP1

• Dentin matrix protein 1 (DMP1) has been known for a number of years to bind to CD44 and ArgGlyAsp sequence-dependent integrins [1].

Regulatory relationships of DMP1

• Dentin matrix protein 1 enhances invasion potential of colon cancer cells by bridging matrix metalloproteinase-9 to integrins and CD44 [1].
• Recombinant human BMP-2 and BMP-4 were capped with inactivated dentin matrix on amputated pulp [21].
• TGF-beta had a negligible effect on collagen mRNA expression or protein synthesis, indicating that TGF-beta alone does not markedly induce dentin matrix formation per se in the human dentin-pulp complex (Palosaari et al., 2001) [22].

Other interactions of DMP1

• In this report, we demonstrate that dentin matrix protein 1 (DMP1), which is localized in the nucleus during early differentiation of odontoblasts, is able to bind specifically with the DSPP promoter and activate its transcription [12].
• Taken together, these data suggest that odontoblasts activated through TLR2 by Gram-positive bacteria LTA are able to initiate an innate immune response by secreting chemokines that recruit immature dendritic cells while down-regulating their specialized functions of dentin matrix synthesis and mineralization [23].
• In contrast with this inflammatory response, gene expression of major dentin matrix components (type I collagen, dentin sialophosphoprotein) and TGF-beta1 was sharply down-regulated in odontoblasts by LTA [23].
• The creation of a yeast artificial chromosome contig of this newly defined interval has allowed us to demonstrate that the critical region encompasses approximately 2 Mb of DNA and that the dentin-specific gene, dentin sialoprotein, maps to this interval within 300 kb of dentin matrix acidic phosphoprotein 1 and bone sialoprotein [24].
• Comparison of the phylogenetic information present in DMP1 with mitochondrial rDNA and nuclear RAG2 genes indicated no significant heterogeneity [25].

Analytical, diagnostic and therapeutic context of DMP1

• A chromatin immunoprecipitation assay confirmed the in vivo association of DMP1 with the DSPP promoter [12].
• In situ hybridization experiments confirmed that DMP1 mRNA is localized in lung cancer cells [2].
• In the present study, DMP1 expression in PMTs and other soft tissue tumors was analyzed immunohistochemically to verify its utility in the differential diagnosis of PMTs [26].
• ELISA results revealed a significant difference in the concentrations of DMP1, PP and DSP between control and root resorption groups [27].
• We first verified the expressions of the alkaline phosphatase (ALP) gene, dentin matrix protein 1 (DMP-1), and dentinsialophosphoprotein (DSPP) by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and consequently discovered the high expressions of these genes [28].

References