Dentin Matrix Protein 1, a Target Molecule for Cbfa1 in Bone, Is a Unique Bone Marker Gene

Feng, Jian Q.; Zhang, Jianghong; Dallas, Sarah L.; Lu, Yongbo; Chen, Shuo; Tan, Xiaoyu; Harris, S. E.; MacDougall, Mary

doi:10.1359/jbmr.2002.17.10.1822

Cited by 141 publications

(135 citation statements)

References 34 publications

(63 reference statements)

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“…Bone Histology-For histological analyses, knee joints of distal femur and proximal tibia were fixed in 4% formaldehyde/PBS (pH 7.2), decalcified, and embedded in paraffin by standard histological procedures as described previously (22). Sections were cut and stained with Safranin O (Sigma), followed by counter-staining with hematoxylin, to visualize proteoglycans (23).…”

Section: Methodsmentioning

confidence: 99%

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

Zheng

Xie

et al. 2004

Journal of Biological Chemistry

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Calbindin (CaBP)-D28k and CaBP-D9k are cytosolic vitamin D-dependent calcium-binding proteins long thought to play an important role in transepithelial calcium transport. However, recent genetic studies suggest that CaBP-D28k is not essential for calcium metabolism. Genetic ablation of this gene in mice leads to no calcemic abnormalities. Genetic inactivation of the vitamin D receptor (VDR) gene leads to hypocalcemia, secondary hyperparathyroidism, rickets, and osteomalacia, accompanied by 90% reduction in renal CaBP-D9k expression but little change in CaBP-D28k. To address whether the role of CaBP-D28k in calcium homeostasis is compensated by CaBP-D9k, we generated VDR/CaBP-D28k double knockout (KO) mice, which expressed no CaBP-D28k and only 10% of CaBP-D9k in the kidney. On a regular diet, the double KO mice were more growth-retarded and 42% smaller in body weight than VDRKO mice and died prematurely at 2.5-3 months of age. Compared with VDRKO mice, the double KO mice had higher urinary calcium excretion and developed more severe secondary hyperparathyroidism and rachitic skeletal phenotype, which were manifested by larger parathyroid glands, higher serum parathyroid hormone levels, much lower bone mineral density, and more distorted growth plate with more osteoid formation in the trabecular region. On high calcium, high lactose diet, blood-ionized calcium levels were normalized in both VDRKO and the double KO mice; however, in contrast to VDRKO mice, the skeletal abnormalities were not completely corrected in the double KO mice. These results directly demonstrate that CaBP-D28k plays a critical role in maintaining calcium homeostasis and skeletal mineralization and suggest that its calcemic role can be mostly compensated by CaBP-D9k.It is well established that calcium homeostasis is primarily maintained by the vitamin D and parathyroid hormone (PTH) 1 endocrine systems. In this regard, the principal role of vitamin D is to regulate calcium transport in the intestine and kidney. Intestinal and renal distal tubular calcium transfer consists of a passive, concentration gradient-dependent paracellular transport and an active, ATP-dependent transcellular transport (1). The latter is largely regulated by vitamin D and is crucial when calcium supply is low. It is believed that the vitamin D-mediated transcellular calcium transport in the duodenum and renal distal tubules involves three sequential steps: entry, intracellular movement, and extrusion. Influx of luminal calcium into the epithelial cells is propelled by a steep electrochemical gradient across the apical membrane, saturable at high levels of luminal calcium, and mediated by apical calcium channels (2-4). Once in the cytosol, calcium binds to the vitamin D-dependent calcium-binding proteins, calbindins (CaBPs), which ferry calcium from the apical to the basolateral portion of the cell, where the Na ϩ /Ca 2ϩ exchanger and Ca 2ϩ -dependent ATPase on the basolateral membrane extrude calcium into extracellular fluids (5-7). It is believed that the apical to b...

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Section: Methodsmentioning

confidence: 99%

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

Zheng

Xie

et al. 2004

Journal of Biological Chemistry

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“…RUNX2, a member of the RUNX transcription factor family, is a transcription factor that is crucial for the regulation of genes that support bone formation 97 and as such it is involved in the control of OPN 98 , BSP 99 , DMP1 (REF. 100) and DSPP 101 expression. All the RUNX proteins are intimately associated with tumour progression, invasion and metastasis 102 .…”

Section: Microcalcificationmentioning

confidence: 99%

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer

et al. 2008

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Numerous components and pathways are involved in the complex interplay between cancer cells and their environment. The family of glycophosphoproteins comprising osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein -small integrin-binding ligand N-linked glycoproteins (SIBLINGs) -are emerging as important players in many stages of cancer progression. From their detection in various human cancers to the demonstration of their key functional roles during malignant transformation, invasion and metastasis, the SIBLINGs are proteins with potential as diagnostic and prognostic tools, as well as new therapeutic targets.

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“…However, the effects of recombinant DMP1 on in vitro mineralization are controversial and depend on phosphorylation state (12). 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).…”

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confidence: 99%

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

Mishina

Chen

et al. 2005

Journal of Biological Chemistry

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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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Dentin Matrix Protein 1, a Target Molecule for Cbfa1 in Bone, Is a Unique Bone Marker Gene

Cited by 141 publications

References 34 publications

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

Critical Role of Calbindin-D28k in Calcium Homeostasis Revealed by Mice Lacking Both Vitamin D Receptor and Calbindin-D28k

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer

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

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