Differential Regulation of Dentin Sialophosphoprotein Expression by Runx2 during Odontoblast Cytodifferentiation

Chen, Shuo; Rani, Sheela; Wu, Yimin; Unterbrink, Aaron; Gu, Tao; Gluhak-Heinrich, Jelica; Chuang, Hui Hsiu; MacDougall, Mary

doi:10.1074/jbc.m502929200

Cited by 154 publications

(154 citation statements)

References 73 publications

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“…These observations suggest that the expression of the specific gene DSPP during dentinogenesis is governed not only by differentially expressed transcription factors and growth factors (61,(66)(67)(68)(69)(70), but also by differentially expressed miRNAs.…”

Section: Discussionmentioning

confidence: 93%

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Huang

Xu²,

Gao³

et al. 2011

Int J Mol Med

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Abstract. Dentin sialophosphoprotein (DSPP), an important marker of odontoblast differentiation, is a prerequisite for tooth development and mineralization; however, the molecular mechanisms of both temporal and spatial regulation remain unknown. MicroRNAs (miRNAs) provide an additional level of control beyond that of transcription factors, which regulate post-transcriptional control of gene expression. The present study was designed to provide a first attempt at an in-depth analysis of dental pulp cells at various odontoblastic differentiation stages to obtain miRNA differential expression patterns, and to determine the contribution of miRNAs in the expression of DSPP during odontoblast differentiation. Dual luciferase reporter assays and qRT-PCR were used to validate miRNAs identified from bioinformatic analyses to determine whether they were able to regulate the DSPP gene in dental pulp cells cultured in a mineralizing medium. The results presented here suggest that DSPP is regulated post-transcriptionally by mir32, mir885-5p and mir586 during odontoblast differentiation.

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Section: Discussionmentioning

confidence: 93%

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Huang

Xu²,

Gao³

et al. 2011

Int J Mol Med

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“…Bone morphogenetic protein/TGF␤ stimulation triggers expression of RUNX2 and its target genes in osteoblasts. However, the same response in odontoblasts is triggered by fibroblast growth factor family of proteins (28). Therefore, it was necessary to study the involvement of GRP-78 in the endocytosis of DMP1 in osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Stress Chaperone GRP-78 Functions in Mineralized Matrix Formation

Ravindran¹,

Gao²,

Ramachandran³

et al. 2011

Journal of Biological Chemistry

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Mineralized matrix formation is a well orchestrated event requiring several players. Glucose-regulated protein-78 (GRP-78) is an endoplasmic reticulum chaperone protein that has been implicated in functional roles ranging from involvement in cancer biology to serving as a receptor for viruses. In the present study we explored the role of GRP-78 in mineralized matrix formation. Differential expression of GRP-78 mRNA and protein was observed upon in vitro differentiation of primary mouse calvarial cells. An interesting observation was that GRP-78 was identified in the secretome of these cells and in the bone matrix, suggesting an extracellular function during matrix formation. In vitro nucleation experiments under physiological concentrations of calcium and phosphate ions indicated that GRP-78 can induce the formation of calcium phosphate polymorphs by itself, when bound to immobilized type I collagen and on demineralized collagen wafers. We provide evidence that GRP-78 can bind to DMP1 and type I collagen independent of each other in a simulated extracellular environment. Furthermore, we demonstrate the cell surface localization of GRP-78 and provide evidence that it functions as a receptor for DMP1 endocytosis in pre-osteoblasts and primary calvarial cells. Overall, this study represents a paradigm shift in the biological function of GRP-78. GRP-78,2 also known as hspa5, is a member of the heat shock protein 70 family. Its primary function is to act as a molecular chaperone in the endoplasmic reticulum (ER) and facilitates the proper folding and assembly of membrane and secretory proteins. However, GRP-78 has been shown to be up-regulated under stress conditions such as the presence of toxic agents (1-4). GRP-78 has been reported to be translocated to the detergent-resistant fractions of the plasma membrane of these cells (5, 6). It has also been implicated to function as a receptor for ␣2-macroglobulin and different viruses through lipid rafts (7-9). Interestingly, GRP-78 has been shown to possess calcium binding properties with reports of calcium binding affinity ranging from 1-2 mol of calcium/mol of GRP-78 to much larger quantities (10). The biological significance of the calcium binding ability of GRP-78 is, however, a subject of debate, with its role primarily being attributed to binding of ER Ca 2ϩ similar to other sequestering proteins.Recent studies have shown that several stress proteins play a significant role in osteoblast differentiation. Specifically, Old Astrocyte Specifically Induced Substance, an ER stress transducer, has been implicated to be involved in bone formation (11). Additionally, a study on the analysis of the secretome of differentiating human mesenchymal stem cells showed an increase in the amount of secreted stress proteins (12). This study quantitatively analyzed the presence of GRP-78 in the secreted pool of proteins and showed that the amount of secreted protein increased when the cells were subjected to in vitro differentiation. Increase in expression of GRP-78 was attributed to...

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“…Thus, BMP2 is involved in specifying the fate of the dental mesenchymal cells. DSPP expression was observed in odontoblasts at the bell stage and continuously through later stages in mouse teeth by in situ hybridization assay (4,5,7). Compared with other tissues such as bone, DSPP is highly expressed in odontoblasts, suggesting its important biological functions during odontogenesis.…”

mentioning

confidence: 96%

“…Recently, it has reported that DSPP extracted from porcine teeth consists of three dentin matrix proteins as follows: DSP, DPP, and dentin glycoprotein, which is located between DSP and DPP domains (14). DSPP is expressed predominantly in odontoblasts and transiently in preameloblasts (4,5). Heterogeneous mutations of human DSPP are associated with dentinogenesis imperfecta type II (DGI-II), type III (DGI-III), and dentin dysplasia type II (DD-II) (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

“…Dentin extracellular matrix is composed of the inorganic components with mostly hydroxyapatite (about 70%) and the organic matrix that consists of collagenous and noncollagenous proteins (NCPs). 2 Among the NCPs, dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) are expressed at high levels in tooth, especially in dentin (4,5). DSP accounts for 5-8% of the NCPs with high carbohydrate and sialic acid levels, whereas DPP is the principal dentin matrix protein with about 50% of the NCPs.…”

mentioning

confidence: 99%

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Bone Morphogenetic Protein 2 Mediates Dentin Sialophosphoprotein Expression and Odontoblast Differentiation via NF-Y Signaling

Chen

Gluhak-Heinrich

Martı́nez

et al. 2008

Journal of Biological Chemistry

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107

100

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Dentin sialophosphoprotein (DSPP), an important odontoblast differentiation marker, is necessary for tooth development and mineralization. Bone morphogenetic protein 2 (BMP2) plays a vital role in odontoblast function via diverse signal transduction systems. We hypothesize that BMP2 regulates DSPP gene transcription and thus odontoblast differentiation. Here we report that expression of BMP2 and DSPP is detected during mouse odontogenesis by in situ hybridization assay, and BMP2 up-regulates DSPP mRNA and protein expression as well as DSPP-luciferase promoter activity in mouse preodontoblasts. By sequentially deleting fragments of the mouse DSPP promoter, we show that a BMP2-response element is located between nucleotides ؊97 and ؊72. Tooth development involves sequential and reciprocal interaction between dental epithelial and mesenchymal cells. The formation of dentin or dentinogenesis originates from the neural crest-derived mesenchymal cells and proceeds in a series of cytodifferentiation stages to form odontoblasts in a specific spatial and temporal pattern originating at the principal cusp tip and advancing toward the base of the tooth (1-3). A consequence of odontoblast cytodifferentiation is the expression of specific gene products that form the dentin extracellular matrix. Dentin extracellular matrix is composed of the inorganic components with mostly hydroxyapatite (about 70%) and the organic matrix that consists of collagenous and noncollagenous proteins (NCPs).2 Among the NCPs, dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) are expressed at high levels in tooth, especially in dentin (4, 5). DSP accounts for 5-8% of the NCPs with high carbohydrate and sialic acid levels, whereas DPP is the principal dentin matrix protein with about 50% of the NCPs. DPP, with high levels of aspartic acid and phosphoserine, is believed to be a nucleator or modulator of function related to dentin mineralization and hydroxyapatite crystal formation (6 -8).

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Differential Regulation of Dentin Sialophosphoprotein Expression by Runx2 during Odontoblast Cytodifferentiation

Cited by 154 publications

References 73 publications

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Stress Chaperone GRP-78 Functions in Mineralized Matrix Formation

Bone Morphogenetic Protein 2 Mediates Dentin Sialophosphoprotein Expression and Odontoblast Differentiation via NF-Y Signaling

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