Disease relevance of Dmp1

• Expression of DMP1 mRNA in osteocytes increased 2-fold as early as 6 h after treatment in both the bone formation and bone resorption sites [1].
• Histological analysis and muCT 3-D images suggested that dmp1 KO mice had osteomalacia [2].
• Karyotypic analyses of MEFs and lymphomas from DMP1-null animals revealed pseudodiploid chromosome numbers, consistent with the retention of wild-type p53 [3].
• CONCLUSIONS: PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying [4].
• METHODS: PP transgenic mice were created by using mouse PP complementary DNA under the control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter (pCAGGS expression vector) [4].

High impact information on Dmp1

• We disrupted sequences encoding the DNA-binding domain of DMP1 in mouse embryonic stem cells and derived animals lacking the functional protein [3].
• The DMP1 transcription factor induces the ARF tumor suppressor gene in mouse fibroblasts, leading to cell cycle arrest in a p53-dependent manner [3].
• RESULTS: A unique line of transgenic mice was created that overexpresses PP in the pancreatic islets with low levels of expression in other tissues including the brain [4].
• The remaining PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared with controls, a result that was more evident in male than in female mice [4].
• Induction of p19(Arf) and p21(Cip1) by oncogenic Raf was compromised in Dmp1-null cells, which were resistant to Raf-mediated premature senescence [5].

Biological context of Dmp1

• Taken together, these studies suggest that DMP-1 is essential for later dentinogenesis during postnatal development [6].
• In vitro promoter studies were performed using plasmid constructs containing mouse DMP-1 and DSPP promoter sequences fused to the luciferase reporter gene [7].
• Transient transfection studies demonstrate for the first time that TGF beta-1 downregulates both DMP-1 and DSPP genes [7].
• Whereas no apparent abnormalities were observed in prenatal bone development, Dmp1-deficient (Dmp1(-/-)) mice unexpectedly develop a severe defect in cartilage formation during postnatal chondrogenesis [8].
• To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene [9].

Anatomical context of Dmp1

• In contrast to Dspp expression that was tooth-specific, Dmp1 was expressed by osteoblasts throughout ossification in the skeleton [10].
• Reverse transcription-polymerase chain reaction was performed on embryonic day 13 to 1-day-old first molars using Dmp1- and DSPP-specific primer sets [10].
• The dentin matrix protein-1 (DMP-1) gene is identified in odontoblasts during both embryonic and postnatal development [6].
• Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development [6].
• Dmp and Bsp mRNA was also expressed in the developing testis cords, supporting the view that all three SIBLING proteins may contribute to testis differentiation [11].

Associations of Dmp1 with chemical compounds

• Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared [12].
• During the early phase of osteoblast maturation, Ca(2+) surges into the nucleus from the cytoplasm, triggering the phosphorylation of DMP1 by a nuclear isoform of casein kinase II [13].
• This phosphorylated DMP1 is then exported out into the extracellular matrix, where it regulates nucleation of hydroxyapatite [13].
• Dentin matrix protein 1 (DPM1), present as a processed fragment (57-kD protein) in bone, is seen in dentin on sodium dodecyl sulfate polyacrylamide gel electrophoresis as one intact protein of 150-200 kD [14].
• Dentin matrix protein 1 (DMP1) is an Arg-Gly-Asp-containing acidic phosphoprotein that was originally identified from a rat incisor cDNA library and was thought to be a dentin-specific protein [15].

Enzymatic interactions of Dmp1

• Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family [16].

Regulatory relationships of Dmp1

• TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts [7].
• Intrinsic histone acetyltransferase activity of p300 also plays a critical role in regulating DMP1 gene expression [17].

Other interactions of Dmp1

• Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5 [12].
• This study demonstrates the role of c-fos and c-jun on the transcriptional regulation of DMP1 gene [18].
• Transcriptional regulation of dentin matrix protein 1 by JunB and p300 during osteoblast differentiation [17].
• Earlier we have reported on the transcriptional regulation of DMP1 by c-Fos and c-Jun (AP-1) transcription factors [17].
• Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein whose expression is precisely controlled temporally and spatially during the differentiation of the odontoblasts [18].

Analytical, diagnostic and therapeutic context of Dmp1

• In situ hybridization studies revealed a much broader Dmp1 tissue expression pattern than previously reported [19].
• Studies of fetal rat calvarial (FRC) cell cultures showed that the expression of Dmp1 was associated closely with "bone nodule" formation and mineralization in vitro [20].
• By immunocytochemistry using a C-terminal region peptide antibody to DMP1, we found that there was a transient decrease in immunoreactivity at 3 days after treatment on both the formation side and the resorption side compared with the matched contralateral control tissue [1].
• In this study, we examined the effect of mechanical loading on expression of DMP1 mRNA and DMP1 protein in alveolar bone in the mouse tooth movement model by in situ hybridization and immunocytochemistry [1].
• A DMP-1 DNA probe was generated1using PCR amplification of the mouse full-length DMP-1 and labeled with [32P] d-CTP [21].

References