The Dentin Matrix Protein 1 (Dmp1) is Specifically Expressed in Mineralized, but not Soft, Tissues during Development

Feng, Jianquan; Huang, Haiyang; Lu, Yongbo; Ye, L.; Xie, Yixia; Tsutsui, Takeo W.; Kunieda, Tetsuo; Castranio, Trisha; Scott, Greig; Lf, Bonewald; Mishina, Yuji

doi:10.1177/154405910308201003

Cited by 210 publications

(220 citation statements)

References 21 publications

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“…This conclusion is consistent with immunohistochemical observations showing a cellular distribution of DMP1 predominantly in chicken and rat osteocytes, rather than in osteoblasts (4), and around cell processes in bone and dentin (12). These localization studies, along with results from DMP1 knockout experiments (31), suggest that phosphorylated full-length DMP1 may represent a protective form, preventing pathologic calcification of cells and their processes. Similar functions have been attributed to matrix Gla protein and osteopontin (32,33).…”

Section: Resultssupporting

confidence: 79%

In Vitro Effects of Dentin Matrix Protein-1 on Hydroxyapatite Formation Provide Insights into in Vivo Functions

Tartaix

Doulaverakis

George

et al. 2004

Journal of Biological Chemistry

174

146

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Dentin matrix protein-1 (DMP1) is a mineralized tissue matrix protein synthesized by osteoblasts, hypertrophic chondrocytes, and ameloblasts as well as odontoblasts. DMP1 is believed to have multiple in vivo functions, acting both as a signaling molecule and a regulator of biomineralization. Using a cell-free system in vitro, we evaluated the action of DMP1 in the regulation of hydroxylapatite (HA) formation and crystal growth. The non-phosphorylated recombinant protein acted as an HA nucleator, increasing the amount of mineral formed in a gelatin gel HA growth system relative to protein-free controls. The recombinant protein phosphorylated in vitro had no detectable effect on HA formation and growth. In contrast, phosphorylated bovine DMP1 expressed in marrow stromal cells with an adenovirus vector containing 29.7 phosphates/mol was an effective inhibitor of HA formation and growth. The native full-length protein appeared to be absent or present in only small amounts in the extracellular matrix of bones and teeth. However, two highly phosphorylated fragments representing the N-and C-terminal portions of DMP1 have been identified, apparently arising from proteolytic cleavage of four X-Asp bonds. The highly phosphorylated C-terminal 57-kDa fragment (containing 42 phosphates/mol), like the non-phosphorylated DMP1, was an HA nucleator. These data suggest that, in its native form, DMP1 inhibits mineralization, but when cleaved or dephosphorylated, it initiates mineralization. These in vitro data are consistent with the findings in the DMP1 knockout mouse.Dentin matrix protein-1 (DMP1) 1 is an acidic, phosphorylated, integrin-binding extracellular matrix protein first identified by screening a rat cDNA library (1). Northern blot analysis in the rat originally suggested that the DMP1 message was odontoblast-specific, with in situ hybridization showing DMP1 mRNA expression to be restricted to those fully differentiated odontoblasts engaged in active dentin matrix formation, with transient expression by ameloblasts (1, 2). More recent in situ hybridization studies show a much broader pattern of expression of DMP1, with expression associated with a number of mineralizing tissues, including bone and cementum (3). In rat and chicken bone, immunohistochemical detection showed an association of DMP1 with osteocytes, but not with osteoblasts (4). In the mouse, hypertrophic chondrocytes express more DMP1 than other cell types (5). DMP1 was detected at high levels by Northern analysis in fetal bovine brain and cultured long bone as well as in odontoblasts (6). Most recently, DMP1 was localized by immunohistochemistry in human lung cancer tissue (7).DMP1 is a small protein that has been postulated to have a high affinity for hydroxylapatite (HA) (8,9). This coupled with its localization in mineralized tissues suggested that DMP1 could have an important role in mineralization. DMP1 is a member of the SIBLING (small integrin-binding ligand, Nlinked glycoprotein) family of proteins (10, 11). Like other members of the SIBLING family...

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Section: Resultssupporting

confidence: 79%

In Vitro Effects of Dentin Matrix Protein-1 on Hydroxyapatite Formation Provide Insights into in Vivo Functions

Tartaix

Doulaverakis

George

et al. 2004

Journal of Biological Chemistry

174

146

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“…While the immunohistochemical pattern of DMP1 has been clearly elucidated in mice dentin (Feng et al 2003;Lu et al 2007), no correlative TEM and fluorescence data have been available on human sound dentin. DMP1 accumulates along the peritubular dentin wall of human sound dentin, similarly to what has been previously reported in mice (Lu et al 2007), thus suggesting a functional role in their formation and maintenance (Baba et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical localization of dentin matrix protein 1 in human dentin

Orsini¹,

Ruggeri²,

Mazzoni³

et al. 2009

Eur J Histochem

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Dentin matrix protein 1 (DMP1) is a non-collagenous matrix protein with a recognized role in the formation of mineralized tissues such as dentin. The aim of this study was to analyze the distribution of DMP1 in human dentin by means of immunofluorescence and high-resolution immunogold labeling. Fully developed, sound human dentin specimens were submitted to fluorescence labeling and post-embedding immunolabeling techniques with a rabbit polyclonal antihuman DMP1 antibody followed by corresponding fluorochrome-conjugated or gold-conjugated secondary antibodies. Both immunofluorescence and immunogold labeling showed an intense labeling associated with the peritubular dentin. In addition, at the ultrastructural level, there was also a moderate and diffuse immunoreaction over intertubular dentin, and a weak labeling within predentin which increased in density towards the mineralization front. This study suggests that in adult human teeth, like in rodents, DMP1 is prevalently concentrated at the level of peritubular dentin and this feature is preserved also in fully developed-teeth. These data are consistent with what has been observed in rodents and suggest that DMP1 plays a role in maintenance of the dentin tubular space.

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“…Ϫ/Ϫ Mice Exhibit a Chondrodysplasia-like Phenotype-To determine the role of Dmp1 in skeletal development and growth, we generated Dmp1 Ϫ/Ϫ null (KO) mice (17). The bones of Dmp1 ϩ/Ϫ heterozygote mice were similar to the WT littermates with comparable weight, growth rates, and radiographic and histological appearance, suggesting that the loss of a single copy of the Dmp1 gene has no apparent effect on skeletal development (data not shown).…”

Section: Dmp1mentioning

confidence: 99%

“…Ϫ/Ϫ mice were generated with exon 6 deletion as described previously (17). The control, wild type (WT), heterozygous (Dmp1 ϩ/Ϫ ), and homozygous (Dmp1 Ϫ/Ϫ ) null mice were maintained on a C57BL/6 or CD-1 background.…”

Section: Animals-the Dmp1mentioning

confidence: 99%

“…In vivo, Dmp1 is mainly expressed in mineralizing tissues in cells such as hypertrophic chondrocytes, osteoblasts, and osteocytes (13)(14)(15)(16). First observations showed that Dmp1 Ϫ/Ϫ embryos and newborns displayed no apparent skeletal nor tooth phenotype, suggesting that DMP1 may be redundant or nonessential for early dentinogenesis and osteogenesis (17). However, postnatally, Dmp1 Ϫ/Ϫ mice develop a profound tooth formation defect characterized by a partial failure of maturation of predentin into dentin, enlarged pulp chambers, increased width of the predentin zone with reduced dentin wall thickness and hypomineralization (18).…”

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confidence: 99%

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Dmp1-deficient Mice Display Severe Defects in Cartilage Formation Responsible for a Chondrodysplasia-like Phenotype

Mishina

Chen

et al. 2005

Journal of Biological Chemistry

196

215

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Understanding the molecular mechanisms by which cartilage formation is regulated is essential toward understanding the physiology of both embryonic bone development and postnatal bone growth. Although much is known about growth factor signaling in cartilage formation, the regulatory role of noncollagenous matrix proteins in this process are still largely unknown. In the present studies, we present evidence for a critical role of DMP1 (dentin matrix protein 1) in postnatal chondrogenesis. The Dmp1 gene was originally identified from a rat incisor cDNA library and has been shown to play an important role in late stage dentinogenesis. 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. Vertebrae and long bones in Dmp1-deficient (Dmp1 ؊/؊ ) mice are shorter and wider with delayed and malformed secondary ossification centers and an irregular and highly expanded growth plate, results of both a highly expanded proliferation and a highly expanded hypertrophic zone creating a phenotype resembling dwarfism with chondrodysplasia. This phenotype appears to be due to increased cell proliferation in the proliferating zone and reduced apoptosis in the hypertrophic zone. In addition, blood vessel invasion is impaired in the epiphyses of Dmp1 ؊/؊ mice. These findings show that DMP1 is essential for normal postnatal chondrogenesis and subsequent osteogenesis.

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The Dentin Matrix Protein 1 (Dmp1) is Specifically Expressed in Mineralized, but not Soft, Tissues during Development

Cited by 210 publications

References 21 publications

In Vitro Effects of Dentin Matrix Protein-1 on Hydroxyapatite Formation Provide Insights into in Vivo Functions

In Vitro Effects of Dentin Matrix Protein-1 on Hydroxyapatite Formation Provide Insights into in Vivo Functions

Immunohistochemical localization of dentin matrix protein 1 in human dentin

Dmp1-deficient Mice Display Severe Defects in Cartilage Formation Responsible for a Chondrodysplasia-like Phenotype

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