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PubMed2000

Matrix Gla protein is differentially expressed during the deposition of a calcified matrix by vascular pericytes.

PCR-based subtractive hybridisation was used to identify genes up-regulated when pericytes undergo osteogenic differentiation and deposit a calcified matrix. cDNA pools were generated from confluent pericytes and from pericyte cultures containing calcified nodules. A pericyte cDNA library was screened with the product of the subtraction procedure (calcified minus confluent cDNA) and the majority of the positive clones were identified as matrix Gla protein (MGP). Northern analysis and immunohistochemistry demonstrated that MGP was only expressed by pericytes in calcified nodules. Antibodies to MGP inhibited the deposition of a calcified matrix by pericytes, suggesting that MGP regulates both cell differentiation and calcification.

Amino Acid Sequence↗

PubMed2006

Cloning of matrix Gla protein in a marine cartilaginous fish, Prionace glauca: preferential protein accumulation in skeletal and vascular systems.

Matrix Gla protein (MGP) belongs to the family of vitamin K dependent, Gla containing proteins and, in mammals, birds and Xenopus, its mRNA has been previously detected in bone, cartilage and soft tissue extracts, while the accumulation of the protein was found mainly in calcified tissues. More recently, the MGP gene expression was also studied in marine teleost fish where it was found to be associated with chondrocytes, smooth muscle and endothelial cells. To date no information is available on the sites of MGP expression or accumulation in cartilaginous fishes that diverged from osteichthyans, a group that includes mammals, over 400 million years ago. The main objectives of this work were to study the sites of MGP gene expression and protein accumulation by means of in situ hybridization and immunohistochemistry. MGP mRNA and protein were localized as expected not only in cartilage from branchial arches and vertebra but also in the endothelia of the vascular system as well as in the tubular renal endothelium. The accumulation of MGP in non mineralized soft tissues was unexpected and suggests differences in localization or regulation of this protein in shark soft tissues compared to tetrapods and teleosts. Our results also corroborate the hypothesis that in Prionace glauca, as previously shown in mammals, the MGP protein probably also acts as a calcification inhibitor, protecting soft tissues from abnormal and ectopic calcification.

Amino Acid Sequence↗

PubMed1985

Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein.

The complete amino acid sequence of bovine bone matrix Gla protein (MGP) was determined by automatic sequence analysis of the intact protein and of peptides isolated from tryptic and BNPS-skatole digests. This 79-residue, vitamin K-dependent protein contains a single disulfide bond and 4.8 gamma-carboxyglutamate (Gla) residues, one each at positions 37, 41, 48, and 52, and 0.8 Gla and 0.2 Glu at position 2. There is sufficient sequence homology between MGP and bone Gla protein (BGP) to indicate that these two bovine bone proteins arose by gene duplication and subsequent divergent evolution. Although MGP has a very low solubility in water compared to BGP, there is no hydrophobic domain in MGP which could account for its insolubility, and the overall fraction of hydrophobic residues is 32% for MGP compared to 43% for BGP. MGP is the first vitamin K-dependent protein to be discovered which has several non-gamma-carboxylated residues to the NH2-terminal side of its Gla residues. The presence of NH2-terminal Glu residues between the putative targeting domain for the gamma-carboxylase in the MGP leader sequence and the mid-molecule Gla residues suggests that the gamma-carboxylase may have additional, as yet unrecognized, specificity requirements which determine the susceptibility of Glu residues for gamma-carboxylation.

1-Carboxyglutamic Acid↗

PubMed1986

Developmental appearance of matrix GLA protein during calcification in the rat.

A marked dissociation has been observed between the timed accumulation in calcified tissues of two related vitamin K-dependent proteins, bone Gla protein (BGP) and the recently discovered matrix Gla protein (MGP). In long bone diaphyses, total levels of MGP were essentially equivalent in newborn, juvenile, and adult rats. In agreement with previous studies, BGP levels were only 5% of adult levels in newborn rat bones and increased to 90% of adult levels by 19 days of age. Similar results were obtained from the analysis of the longitudinal distribution of MGP and BGP in 14-day-old rat tibia, a bone in which new mineral is added rapidly at both growth plates. Again, MGP was essentially at the same level in the regions nearest the growth plates as in the midshaft while BGP levels were 10-fold lower in the regions nearest the growth plates. These differences in the timed accumulation of MGP and BGP in calcifying tissues indicate that MGP could function earlier in bone formation than does BGP. To further characterize the MGP antigen in bone, extracts from newborn and adult rat bones were chromatographed by gel filtration over Sephacryl S-200. All of the antigen extracted by formic acid and most of the antigen subsequently extracted by guanidine HCI emerged at the position expected for the 79-residue MGP. There was a significant difference in the fraction of total MGP which was extracted by guanidine HCI in newborn (50%) and adult (20%) bone. The radioimmunoassay for rat MGP which was developed for these studies employs rabbit antibody directed against calf MGP and rat MGP for standards and radioiodinated tracer. This assay has a sensitivity of 0.1 ng and does not detect rat or calf BGP.

Amino Acids↗

PubMed2003

Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular cells.

Expression of matrix GLA protein (MGP), an alleged calcification inhibitor, is increased in calcified arteries. We used calcifying vascular cells (CVC) that form calcified nodules in vitro to clarify the importance of MGP in vascular cell calcification and differentiation. Unexpectedly, MGP dose-dependently increased calcification in CVC. It also increased expression of the osteogenic marker Cbfal, while decreasing expression of the smooth muscle marker alpha-actin as assessed by immunoblotting. Bone morphogenetic protein-2 (BMP-2), a known osteoinductive factor also increased calcification and osteogenic differentiation in CVC. We hypothesized that the effect of MGP was linked to that of BMP-2 since previous studies show that MGP modulates BMP-2 activity. Therefore, we compared the effect of MGP at different levels of exogenous BMP-2. Results showed that high BMP-2 levels significantly increased the stimulatory effect of low levels of MGP. A relative inhibition of calcification was observed at intermediate levels of MGP and a trend towards renewed stimulation at high levels of MGP. Thus, addition of MGP either promoted or inhibited calcification, depending on the relative amounts of BMP-2 and MGP. This was confirmed in human CVC with different relative expression of BMP-2 and MGP. Calcification in CVC with high relative expression of BMP-2 was inhibited by MGP, while calcification in CVC with low relative expression of BMP-2 was stimulated by MGP. MGP and BMP-2 both accelerated nodule formation, but had opposite effects on nodule size; MGP decreased while BMP-2 increased nodule size. The effect of BMP-2 may partly be explained by a BMP-2 induced decrease in MGP expression. Together, our results suggest that the effect of MGP on calcification and osteogenic differentiation is determined by availability of BMP-2.

Animals↗

PubMed2004

Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography.

Matrix Gla protein (MGP) is an extracellular matrix protein with wide tissue distribution. It has been demonstrated that the expression of MGP is detected not only in the normal blood vessels but also calcified atherosclerotic plaques, and that MGP deficient mice develop extensive arterial calcification. MGP is thought to be a regulator of vascular calcification. A recent clinical study demonstrates the association between polymorphisms of the MGP gene and increased risk of myocardial infarction. However, there are no reports of the relationship between serum MGP levels and coronary artery calcification (CAC). We evaluated the severity of CAC using electron-beam computed tomography (EBCT), and measured serum MGP levels by enzyme-linked immunosorbent assay in 115 subjects with suspected coronary artery disease. CAC scores were correlated with traditional risk factors, such as age, gender, hyper-tension, diabetes, hyperlipidemia and smoking. The serum MGP levels were lower in patients with CAC than in those without CAC (p<0.001). As the severity of CAC increased, there was a significant decrease in serum MGP levels. Serum MGP levels (U/L) were 116.7 +/- 20.3, 104.9 +/- 19.2, 95.2 +/- 15.2 and 82.2 +/- 19.7, (medians 115.5, 105.0, 94.8, and 81.9) for the subjects with normal (CAC score=0), mild (CAC score=1 to 99), moderate (CAC score=100 to 400), and severe (CAC score >400) coronary calcification, respectively. We found that serum MGP levels are inversely correlated with the severity of CAC. These data suggest a possible role for MGP in the development of vascular calcification.

Aged↗

PubMed2000

Matrix gla protein is regulated by a mechanism functionally related to the calcium-sensing receptor.

Matrix Gla protein (MGP) is a mineral binding extra-cellular matrix protein which is thought to be a key inhibitor of tissue and vascular calcification. It is known to be upregulated in areas of extracellular calcification possibly to limit further harmful calcification. In this study we have demonstrated that extracellular ionic calcium (high levels of which induce calcification) is a key signal for MGP regulation and that this effect is mediated by a G protein mediated cation-sensing mechanism, functionally related to, but molecularly distinct from the calcium-sensing receptor. We therefore propose that this novel cation sensing mechanism may play a homeostatic role in preventing pathological calcification.

Animals↗

PubMed1992

Cell adhesion to matrix Gla protein and its inhibition by an Arg-Gly-Asp-containing peptide.

Matrix Gla protein (MGP) is a 14-kDa protein found in bone and cartilage which contains the unusual amino acid gamma-carboxyglutamic acid (Gla). The biological function of this protein has not been elucidated. Here we have demonstrated the adherence of chondrocytes, fibroblasts, osteosarcoma cells, and kidney mesangial cells to MGP purified from bovine bone. Maximum adherence occurred at MGP concentrations of 0.5-1.0 micrograms/ml. Removal of the calcium-binding Gla residues by thermal decarboxylation of MGP destroyed the proteins' cell adherence properties. Cell adherence to MGP was not affected by the presence of antibodies directed against the C-terminal (non-Gla) portion of the protein or the presence of cycloheximide during the adherence assay. However, the Arg-Gly-Asp-containing synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro significantly inhibited cell attachment to MGP, whereas the control peptide Gly-Arg-Gly-Glu-Ser-Pro had minimal effect. These data indicate that MGP may function in mediating cell attachment to the extracellular matrix via a receptor that requires intact Gla residues and that can be inhibited by Arg-Gly-Asp-containing peptides.

Amino Acid Sequence↗

PubMed1987

Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase.

Matrix Gla protein (MGP), a low molecular weight protein found in bone, dentin, and cartilage, contains 5 residues of the vitamin K-dependent amino acid gamma-carboxyglutamic acid (Gla). We have used antibodies raised against MGP and oligonucleotide probes to screen a lambda gt11 cDNA library constructed from the rat osteosarcoma cells (line ROS 17/2) that had been pretreated with 1 alpha,25-dihydroxyvitamin D3. By sequencing several cloned cDNAs, we established a 523-base-pair sequence that predicts an 84-residue mature MGP and a 19-residue hydrophobic signal peptide. The 84-residue mature rat MGP predicted from the cDNA sequence has an additional 5 residues at its C terminus (-Arg-Arg-Gly-Ala-Lys) not seen in the sequence of MGP isolated from bovine bone. The structure of rat MGP provides insight into the mechanisms by which the vitamin K-dependent gamma-carboxylase recognizes substrate. The present studies show that MGP, unlike other vitamin K-dependent proteins, lacks a propeptide. The absence of an MGP propeptide demonstrates that gamma-carboxylation and secretion of vitamin K-dependent proteins need not be linked to the presence of a propeptide or to its proteolytic removal. The propeptides of other vitamin K-dependent proteins are structurally homologous, and there is evidence that this homologous propeptide domain is important to substrate recognition by the gamma-carboxylase. Mature MGP has a sequence segment (residues 15-30) that is homologous to the propeptide of other vitamin K-dependent proteins and probably serves the same role in gamma-carboxylase recognition. Rat MGP also has a second sequence that has recently been identified in all known vitamin K-dependent vertebrate proteins, the invariant unit Glu-Xaa-Xaa-Xaa-Glu-Xaa-Cys (EXXXEXC). Since the glutamic residues in this unit are sites of gamma-carboxylation, it has been suggested that the EXXXEXC unit could allow the gamma-carboxylase to discriminate between substrate and product. The demonstration that two structures common to vitamin K-dependent proteins, the homologous propeptides domain and the invariant EXXXEXC unit, are in mature MGP indicates that des-gamma-carboxy-MGP should be an excellent in vitro gamma-carboxylase substrate for analysis of mechanisms involved in substrate recognition and product dissociation.

Amino Acid Sequence↗

PubMed2006

Excess magnesium inhibits excess calcium-induced matrix-mineralization and production of matrix gla protein (MGP) by ATDC5 cells.

We found that excessive extracellular Ca2+ and/or Mg2+ affected the process of matrix mineralization and glycosaminoglycan (GAG) production by cells of the prechondrogenic cell line, ATDC5. Excess Ca2+ induced both matrix mineralization and GAG production in the cells. On the other hand, excess Mg2+ reduced this Ca2+-mediated rise in both mineralization and GAG production in them. Next we measured the mRNA levels of cartilage-associated genes such as calcium-sensing receptor (CaSR), matrix gla protein (MGP), bone gla protein (BGP), and Runt-related transcription factor 2 (Runx2) in ATDC5 cells. Excess Ca2+ increased the MGP, BGP, and CaSR mRNA levels, and excess Mg2+ reduced the Ca2+-induced increase in the MGP mRNA level in the cells. The changes in the MGP mRNA level paralleled those in the MGP protein level. These data show that Ca2+ and Mg2+ regulated the matrix mineralization positively and negatively, respectively, in ATDC5 cells and suggest that excess Mg2+ might inhibit the excess Ca2+-promoted mineralization mediated by MGP induction in chondrocytes.

Animals↗

PubMed1997

Matrix Gla protein gene expression is induced by transforming growth factor-beta in embryonic lung culture.

Matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein with a wide tissue distribution. The current study was designed to investigate the possible regulation of MGP by exogenous transforming growth factor-beta (TGF-beta) during lung development. Using reverse transcription coupled competitive polymerase chain reaction methodology, we determined that exogenous TGF-beta 1 increases MGP mRNA levels in embryonic mouse lung culture in a concentration-dependent manner. MGP mRNA levels were elevated by 5.0-fold at 50 ng/ml TGF-beta 1 in E11 embryonic mouse lungs explanted for 4 days in serumless culture. MGP mRNA stimulation by TGF-beta 1 was a time-dependent event: MGP message increment was initially detected after 1 day in culture, and MGP mRNA levels continued to increase up to 4 days in the presence of TGF-beta 1. In addition, embryonic lungs in serumless medium without exogenously added TGF-beta 1 showed an increase, although to a lesser extent, in pulmonary MGP mRNA level during culture, indicating that MGP expression is also developmentally regulated. The present results indicate that MGP gene expression can be stimulated by exogenous TGF-beta 1 during early embryonic mouse lung branching morphogenesis in culture.

Animals↗

PubMed2003

Matrix Gla protein gene expression and protein accumulation colocalize with cartilage distribution during development of the teleost fish Sparus aurata.

Matrix Gla protein (MGP) is a member of the family of extracellular mineral-binding Gla proteins, expressed in several tissues with high accumulation in bone and cartilage. Although the precise molecular mechanism of action of this protein remains unknown, all available evidence indicates that MGP plays a role as an inhibitor of mineralization. We investigated the sites of gene expression and protein accumulation of MGP throughout development of the bony fish Sparus aurata, by in situ hybridization, Northern and RT-PCR Southern hybridization, and immunohistochemistry. The results obtained were compared with the patterns of developmental appearance of cartilaginous and mineralized structures in this species, identified by histological techniques and by detection of mRNA presence and protein accumulation of osteocalcin (Bone Gla protein), a marker for osteoblasts known to accumulate in bone mineralized extracellular matrix. The expression of MGP mRNA was first detected at 2 days posthatching (dph) by Northern analysis, RT-PCR amplification, and in situ hybridization, and thereafter continuously detected at various levels of intensity, until 130 dph. In situ hybridization analysis performed in parallel with immunohistochemistry indicated that until ca. 45 dph, the MGP gene was highly expressed in a number of different tissues including skull, jaw, neural and hemal arches, and heart and the protein accumulated in cartilaginous tissues. At 85 dph, a stage when most skeletal structures are mineralized, MGP gene expression and protein accumulation were restricted to the remaining cartilaginous structures, whereas osteocalcin gene expression and protein accumulation were localized in most mineralized structures. MGP gene expression was also detected in heart and kidney, although in situ hybridization only detected MGP mRNA in heart, located in the arterial bulbus and not in the cardiac muscle. Our results are in agreement with those recently described for MGP localization in adult tissues of another teleost fish, as well as available data from higher vertebrates, strengthening the hypothesis of a conserved function for MGP from teleost fish to human, a period of more than 200 million years of evolution. In addition, Sparus aurata, a marine teleost fish routinely grown in captivity, appears to be a good model to further analyze MGP gene expression and regulation.

Amino Acid Sequence↗

PubMed2004

T-138C polymorphism of matrix gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification.

Matrix Gla protein (MGP) is a crucial inhibitor of vessel and cartilage calcification. We investigated the association of T-138C MGP promoter polymorphism with the degree of atherosclerosis, vascular calcification and patients' clinical background including calcification of the trachea and costal cartilage. Analysis of 108 autopsy cases was carried out by polymorphism-specific PCR on formalin-fixed paraffin-embedded samples. Statistical correlations among eight risk factors and five markers related to atherosclerosis and extra-bone tissue calcification were multivariantly analyzed. We found very high canonical correlations between the factors and the markers, and Pearson's correlation analysis revealed six significant correlations between age and the Gore index; age and costal cartilage calcification; sex and costal cartilage calcification; hypertension and the Gore index; hypertension and the calcification factor of the Gore index; and hyperlipidemia and costal cartilage calcification. The promoter activity of the -138T allele was significantly higher than that of the -138C allele; treatment with 12-O-tetradecanonylphorbol 13-acetate (TPA) significantly activated the former, but had almost no effect on the latter. The C genotype was significantly common among Japanese subjects, (TT 45.5%, TC 37.6% and CC 16.8%) compared with that reported in the Netherlands, Northern Ireland and France. No significant correlation was observed, however, between T-138C MGP promoter polymorphism and the markers. Although the C genotype (TC+CC) tended to show a higher calcification factor than the TT genotype, no significant difference was observed among the genotypes in the Gore index or in the calcification factor. Although MGP promoter activity and the binding of the AP-1 transcription factor were clearly different between T-138 and C-138 MGP promoter polymorphism in vitro, T-138C polymorphism was, statistically, not an independent factor of atherosclerosis or atherosclerotic vascular calcification in the abdominal aorta.

Adolescent↗

PubMed1991

Carboxyl-terminal proteolytic processing of matrix Gla protein.

The present study was undertaken to determine the extent of COOH-terminal proteolytic processing in matrix Gla protein (MGP), a 10-kDa protein which contains 5 residues of the vitamin K-dependent Ca2+ binding amino acid, gamma-carboxyglutamic acid (Gla). Two forms of MGP were isolated from demineralization and urea extracts of bovine cortical bone, one 79 residues in length with the COOH terminus Phe-Arg-Gln and the other 83 residues in length with the COOH terminus Phe-Arg-Gln-Arg-Arg-Gly-Ala. The 84-residue form of bovine MGP predicted from the message structure could not be detected in the bone extracellular matrix extracts, and it therefore seems probable that the lysine at position 84 was removed by the action of a carboxypeptidase B-like enzyme prior to secretion. A plausible sequence of proteolytic cleavages that could generate the 79-residue form of MGP would be a trypsin-like cleavage at Arg80-Arg81 or Arg81-Gly82 followed by carboxypeptidase B-like cleavage to remove COOH-terminal arginine(s). Since essentially equal amounts of the 79- and 83-residue forms of MGP were also detected in bovine articular cartilage and plasma, it seems likely that the COOH-terminal processing events identified in bone apply to many of the other tissues which synthesize this protein. Only one form of MGP was detected in human bone extracts, a 77-residue protein that lacks the COOH-terminal residues Arg-Lys-Arg-Arg-Gly-Thr-Lys. This shortened version of human MGP is consistent with the proposed model for COOH-terminal processing, since the amino acid substitution in the COOH terminus of the human protein, Lys79 for Gln79, would allow removal of the additional basic residues from the human MGP COOH terminus by the action of the carboxypeptidase B-like enzymic activity. Recent studies have shown that MGP is strongly induced by retinoic acid in fibroblasts, chondrocytes, and osteoblasts, a response which suggests that MGP mediates an action of retinoic acid on an aspect of cell growth or differentiation. If this hypothesis is true, the present evidence for complex COOH-terminal processing events could provide a means to regulate the as yet unknown activity of MGP in the extracellular environment in a mechanism similar to the activation of hormones such as anaphlotoxins and kinins.

1-Carboxyglutamic Acid↗

PubMed2002

Matrix Gla protein binding to hydroxyapatite is dependent on the ionic environment: calcium enhances binding affinity but phosphate and magnesium decrease affinity.

Matrix Gla protein (MGP) is an inhibitor of mineralization found in bone, cartilage, developing tissues, smooth muscle, and atherosclerotic plaques. MGP interaction with hydroxyapatite (HA) has been inferred by its function, but has never been measured directly. In this study, the influence of MGP antibody (x-MGP) binding, plasmin digestion, and various ions, including calcium and phosphate, on (125)I-labeled MGP-HA binding was examined. Nonlinear regression analysis of MGP binding yielded K(a) (association constant; approximately 8.0 x 10(4) M(-1)) and B(max) (maximum specific bound fraction of MGP; approximately 0.53). Anti-MGP antiserum reduced K(a) to less than half of control (0.33% x-MGP). Plasmin-digested MGP decreased HA binding parameters by almost a third, showing that protein binding and limited proteolysis greatly affected HA binding. The presence of free calcium ions significantly increased binding in a dose-dependent manner, with approximately 1 mmol/L calcium increasing K(a) by a factor of 2. Phosphate ions decreased binding significantly in a dose-dependent fashion, with approximately 1 mmol/L PO(4) decreasing K(a) by a third. Magnesium at approximately 1 mmol/L decreased K(a) significantly by half, but the effect was not dose-dependent. Carbonate, sulfate, and sodium ions had no significant effect on binding. MGP binding to HA is sensitive to protein binding, limited proteolysis, and the surrounding ionic environment.

Anions↗

PubMed1990

Induction of matrix Gla protein synthesis during prolonged 1,25-dihydroxyvitamin D3 treatment of osteosarcoma cells.

The synthesis of matrix Gla protein (MGP) and bone Gla protein (BGP) have been shown to be mutually exclusive in all osteosarcoma cell lines investigated. In the cell lines that produce the respective proteins, synthesis is stimulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) within the first several hours of hormone treatment. In the present studies we have investigated the effects of longer-term treatment with 1,25(OH)2D3 in the ROS 17/2 cell line, a cell line that synthesizes BGP constitutively but does not synthesize MGP. In agreement with earlier studies, the rate of BGP synthesis increases within 8 hours of hormone treatment, is maximal by 24 hours, and remains at the maximal rate through 48 hours of 1,25(OH)2D3 treatment. The present study is the first to report that the rate of BGP secretion at times beyond 48 hours declines to that of control cultures despite the continued administration of 1,25(OH)2D3, and that MGP synthesis is induced in ROS 17/2 cells by 48 hours of 1,25(OH)2D3 treatment. At this time, MGP mRNA could be detected by northern blot analysis and MGP secretion could be demonstrated by radioimmunoassay of culture medium. Both the level of MGP message per unit total RNA and the rate of MGP secretion into culture medium increased steadily between 2 and 6 days of 1,25(OH)2D3 treatment. The MGP synthesized by the 1,25(OH)2D3-treated ROS 17/2 cells was identical to that found in bone by northern blot analysis of message and by western blot analysis of the media antigen. Half-maximal induction of MGP synthesis was obtained with 0.3 nM 1,25(OH)2D3, a 60-fold higher dosage than was required for the half maximal stimulation of BGP synthesis in these cells. Treatment of ROS 17/2 cells with 24,24-F21,25(OH)2D3 suggests that the observed difference in dose dependence is not due to an increased rate of hormone catabolism.

Animals↗

PubMed1998

Expression of matrix Gla protein (MGP) in an in vitro model of vascular calcification.

To investigate the role of matrix Gla protein (MGP), which can bind mineral ions through gamma-carboxylated glutamic acid residues, in vascular calcification, we examined the expression of MGP in an in vitro calcification model by using bovine vascular smooth muscle cells (BVSMC). The expression of MGP mRNA was decreased during BVSMC calcification and its levels were inversely correlated with the quantities of BVSMC calcification. MGP mRNA expression was restored to the level of uncalcified control by inhibiting BVSMC calcification with bisphosphonates. These data suggest that the expression of MGP gene is modulated in the development of vascular calcification.

Alendronate↗

PubMed1993

Differential regulation of matrix Gla protein (MGP) gene expression by retinoic acid and estrogen in human breast carcinoma cells.

Expression of matrix Gla protein (MGP) gene and its regulation by retinoic acid (RA) and estrogen was investigated in eight human breast cancer cell lines. The promoter region of the MGP gene contains a consensus retinoic acid response element (RARE) and the MGP gene expression has been shown to be strongly induced by RA in other systems. Our results suggest that RA negatively regulates MGP mRNA expression in human breast cancer cells that have high levels of estrogen receptors (ER), i.e. MCF-7, ZR-75 and BT474 and positively regulates its expression in cells with either no ERs, i.e. MDA-MB-468 or very low levels of ERs, i.e. T47D. This indicates that ER levels may affect RA modulation of MGP gene expression in human breast cancer cells. The inhibitory effect of RA on MGP gene expression was abolished in RRO-I, the RA-resistant MCF-7 subline. We also demonstrate for the first time that estrogen strongly induces MGP gene expression in ER-positive cells and that estrogen-mediated induction of MGP is blocked by RA even in otherwise RA-resistant cells.

Amino Acid Sequence↗