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

Nakatani, Sachie; Miyata, Hiroshi; Ryanghyok, I.M.; Shimizu, Jun; Wada, Masahiro

doi:10.1016/j.bbrc.2006.07.180

Cited by 28 publications

(27 citation statements)

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“…However, to date, only a limited number of experimental studies performed in animals have confirmed these findings, whereas the majority investigated the role of lowering dietary magnesium on VC (13,14). Thus far, only 2 studies have reported that magnesium has a favorable effect on bone matrix mineralization in an in vitro model (15,16). Therefore, the present study aimed to investigate whether increasing magnesium concentrations influence calcification of rat aortic vascular smooth muscle cells (RAVSMCs).…”

Section: Introductionmentioning

confidence: 91%

Magnesium prevents β-glycerophosphate-induced calcification in rat aortic vascular smooth muscle cells

Bai

Zhang

et al. 2015

Biomedical Reports

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Abstract. Vascular calcification (VC), in which high serum phosphate plays a critical role, is one major problem in patients with chronic kidney disease. Clinical studies report that magnesium has a protective effect on VC. However, the studies regarding the impact of high serum magnesium on VC at a cellular level are few and require further investigation. Therefore, the present study explored the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in rat aortic vascular smooth muscle cells (RAVSMCs). In the present study, the addition of magnesium decreased calcium deposition, which was increased by BGP. Higher magnesium levels inhibited BGP-induced alkaline phosphatase (ALP) activity and decreased the expression of core-binding factor α-1 (Cbfα1). In conclusion, higher magnesium levels prevented BGP-induced calcification in RAVSMCs and inhibited the expression of Cbfα1 and ALP. Thus, magnesium is influencing the expression of Cbfα1 and ALP associated with VC and may have the potential to serve as a role for VC in clinical situations.

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Section: Introductionmentioning

confidence: 91%

Magnesium prevents β-glycerophosphate-induced calcification in rat aortic vascular smooth muscle cells

Bai

Zhang

et al. 2015

Biomedical Reports

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“…However, so far, only a limited number of experimental studies, mostly performed in animals have confirmed these findings, whereas the majority investigated the role of lowering dietary magnesium on VC [10–12]. To date, only one group has investigated the role of magnesium in an in vitro model in a prechondrogenic cell line and reported a favourable effect of magnesium on bone matrix mineralization [13]. However, the effect of magnesium on calcification has not yet been studied in in vitro models.…”

Section: Introductionmentioning

confidence: 99%

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

Kırçelli

Peter

et al. 2011

Nephrology Dialysis Transplantation

146

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Background.Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs).Methods.BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription–polymerase chain reaction and annexin V staining, respectively.Results.Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification.Conclusions.Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations.

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“…Indeed, several VOCs were described as being expressed in chondrocytes, such as N-VOCs (11) and L-and T-VOCs (12). Another possible mechanism could be related to the activation of the calcium-sensing receptor (CaSR), a G protein-coupled receptor (13). Furthermore, calcium was described as stimulating the activity of the transcription factor SP1 (specific protein 1), which increased the basal transcription of ␤1,3-glucuronosyltransferase I, a key enzyme responsible for the completion of cartilage proteoglycans (14).…”

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confidence: 99%

Calcium Input Potentiates the Transforming Growth Factor (TGF)-β1-dependent Signaling to Promote the Export of Inorganic Pyrophosphate by Articular Chondrocyte

Cailotto

Reboul

Sébillaud

et al. 2011

Journal of Biological Chemistry

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Transforming growth factor (TGF)-␤1 stimulates extracellular PP i (ePP i ) generation and promotes chondrocalcinosis, which also occurs secondary to hyperparathyroidism-induced hypercalcemia. We previously demonstrated that ANK was upregulated by TGF-␤1 activation of ERK1/2 and Ca 2؉ -dependent protein kinase C (PKC␣). Thus, we investigated mechanisms by which calcium could affect ePP i metabolism, especially its main regulating proteins ANK and PC-1 (plasma cell membrane glycoprotein-1). We stimulated articular chondrocytes with TGF-␤1 under extracellular (eCa 2؉ ) or cytosolic Ca 2؉ (cCa 2؉ ) modulations. We studied ANK, PC-1 expression (quantitative RT-PCR, Western blotting), ePP i levels (radiometric assay), and cCa 2؉ input (fluorescent probe). Voltage-operated Ca 2؉ -channels (VOC) and signaling pathways involved were investigated with selective inhibitors. Finally, Ank promoter activity was evaluated (gene reporter). TGF-␤1 elevated cCa 2؉ and ePP i levels (by up-regulating Ank and PC-1 mRNA/proteins) in an eCa 2؉ dose-dependent manner. TGF-␤1 effects were suppressed by cCa 2؉ chelation or L-and T-VOC blockade while being mostly reproduced by ionomycin. In the same experimental conditions, the activation of Ras, the phosphorylation of ERK1/2 and PKC␣, and the stimulation of Ank promoter activity were affected similarly. Activation of SP1 (specific protein 1) and ELK-1 (Ets-like protein-1) transcription factors supported the regulatory role of Ca 2؉ . SP1 or ELK-1 overexpression or blockade experiments demonstrated a major contribution of ELK-1, which acted synergistically with SP1 to activate Ank promoter in response to TGF-␤1. TGF-␤1 promotes input of eCa 2؉ through opening of L-and T-VOCs, to potentiate ERK1/2 and PKC␣ signaling cascades, resulting in an enhanced activation of Ank promoter and ePP i production in chondrocyte.The balance between extracellular inorganic pyrophosphate (ePP i ) 3 and extracellular inorganic phosphate (eP i ) is critical for homeostasis of articular cartilage. Indeed, an increase in ePP i supports calcium pyrophosphate dihydrate crystal (CPPD) depositions responsible for articular chondrocalcinosis (ACC) (1). Production of ePP i by articular chondrocytes is dependent on PC-1 (plasma cell membrane glycoprotein-1; also known as ENPP1), an ectoenzyme that produces ePP i from nucleotide triphosphates (2), and on the transporter ANK, which exports PP i across the cell membrane (3). Although ePP i level can be controlled by tissue-nonspecific alkaline phosphatase, which hydrolyzes ePP i into eP i , no expression of this enzyme was detected in healthy articular cartilage compared with osteoarthritic cartilage (4). Therefore, CPPD formation only depends on the expression level of PC-1 and ANK in mature articular cartilage. Transforming growth factor (TGF)-␤1 is a well known inducer of ePP i production by articular chondrocytes (1). We demonstrated previously that ANK was the major contributor of this TGF-␤1-induced ePP i production; meanwhile, PC-1 played a minor role (5). Furthermo...

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

Cited by 28 publications

References 34 publications

Magnesium prevents β-glycerophosphate-induced calcification in rat aortic vascular smooth muscle cells

Magnesium prevents β-glycerophosphate-induced calcification in rat aortic vascular smooth muscle cells

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

Calcium Input Potentiates the Transforming Growth Factor (TGF)-β1-dependent Signaling to Promote the Export of Inorganic Pyrophosphate by Articular Chondrocyte

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