Disease relevance of DSPP

• In this study, we sought to evaluate the expression of DSPP in human prostate cancer [1].
• High grade prostatic intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression levels that were similar to those found in neighboring cancer glands [1].
• 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 [2].
• Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP [3].
• We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39) [3].

Psychiatry related information on DSPP

• Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses [4].
• Subjects were separated in two groups by scores for DPP of the Mini-Mult, an abbreviated version of the Minnesota Multiphasic Personality Inventory [5].
• Fifteen persons with discrete social phobia without any personality disorder (DSP), 28 persons with generalized social phobia (GSP) without any personality disorder, 24 persons with GSP with a single diagnosis of avoidant personality disorder (APD), and 23 persons with GSP with more than one PD were included in the present study [6].

High impact information on DSPP

• DSPP mutation in dentinogenesis imperfecta Shields type II [7].
• Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice [3].
• Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization [3].
• In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein [3].
• We identified a nonsense mutation (Gln45stop) in exon 3 of the dentin sialophosphoprotein (DSPP) gene in a Chinese family with dentinogenesis imperfecta Shields type II (DGI-II), in which the affected members showed discoloration and severe attrition of their teeth, with obliterated pulp chambers [7].

Biological context of DSPP

• During dentinogenesis, DSPP is proteolytically cleaved into smaller subunits [8].
• In vivo, DSPP expression was associated with tooth terminal epithelial-mesenchymal interaction events, amelogenesis and dentinogenesis [9].
• The purpose of this study was to perform refined mapping of DSPP related to these disease loci by gene content mapping, as well as to place the DSPP gene on the physical map of human chromosome 4 by sequence tagged site (STS) content mapping [10].
• The genomic organization of human DSPP is very similar to that of mouse, containing five exons and four introns, suggesting it is a homologue of mouse dentin sialophosphoprotein (DSPP) [11].
• Although no function has been ascribed to AG1 or DSP, they should prove to be important markers for the odontoblast phenotype [12].

Anatomical context of DSPP

• Dentin sialophosphoprotein (DSPP) is a major secretory product of odontoblasts and is critical for proper tooth dentin formation [8].
• 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 [13].
• We defined the exact DSPP cleavages that are catalyzed by proteases during crown formation by isolating DSPP-derived proteins from developing porcine molars and characterizing their N-terminal sequences and apparent size on SDS-PAGE and Western blots [8].
• Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively [14].
• The presence of DSPP has been recently established in salivary glands, indicating that its expression is not restricted to mineralized tissues [1].

Associations of DSPP with chemical compounds

• We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue [2].
• Dentin phosphoprotein (DPP) is rich in aspartic acid (D) and phosphoserine (S*) and binds large amounts of calcium [15].
• Dentin sialoprotein (DSP), found only in dentin, is a 53 kDa glycoprotein rich in aspartic acid, serine, glutamic acid and glycine [15].
• With Western immunoblots, we detected DSP in the Gdm/EDTA extracts of rat long bone, at a level of about 1/400 of that in dentin [16].
• DPP is extremely acidic and is rich in aspartic acid and serine [11].

Regulatory relationships of DSPP

• Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation [13].
• We then measured the expression of mRNA encoding dentin sialophosphoprotein (DSPP) as a marker of odontoblasts in rhBMP-2-stimulated human pulp cells using a quantitative polymerase chain reaction [17].

Other interactions of DSPP

• Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth [9].
• Dentin Sialophosphoprotein Is Processed by MMP-2 and MMP-20 in Vitro and in Vivo [8].
• Dentin sialophosphoprotein (DSPP) is an extracellular matrix, prototypical dentin, and a bone-specific gene, however, the molecular mechanisms by which it is temporally and spatially regulated are not clear [13].
• Defects in the human gene encoding DSPP cause inherited dentin defects, and these defects can be associated with bilateral progressive high-frequency sensorineural hearing loss [18].
• Ten of them were already identified in odontoblasts such as DSPP, BSP, enamelysin and Col1A1 [19].

Analytical, diagnostic and therapeutic context of DSPP

• A chromatin immunoprecipitation assay confirmed the in vivo association of DMP1 with the DSPP promoter [13].
• Immunohistochemistry was performed on 69 prostate cancer specimens using LFMb-21 anti-DSPP monoclonal antibody [1].
• In addition, in situ hybridization was used to assess the presence of DSPP mRNA [1].
• 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 [20].
• RESULTS: Both cell cultures expressed DSPP under the conditions of the present experiment [21].

References