Direct Effect of Vitamin D Metabolites on Matrix Vesicle Alkaline Phosphatase

Schwartz, Zvi; Boyan, Barbara D.; Schlader, D. L.; Ramirez, Vanessa I.

doi:10.1515/9783110846713.441

Cited by 2 publications

(7 citation statements)

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“…esis is supported by the fact that 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 cause rapid membrane-and cell maturaChondrocyte cultures tion-dependent changes in the fluidity of chondrocyte cellular and matrix vesicle membranes (Swain et al, The culture system has been described previously in 1993). Which of these explanations is responsible for detail (Boyan et al, 1988b). Resting zone (reserve zone) the observed effects in vivo or in organ or cell culture and growth zone (prehypertrophic and upper hypertrois very difficult to determine because of the presence phic zones) chondrocytes were isolated from the costoof the VDR and its resultant genomic consequences.…”

Section: Synthesis Of Vitamin D Analoguesmentioning

confidence: 99%

“…In addition, 1,25-(OH) 2 D 3 has been shown to modulate mRNA sta-isolated matrix vesicles are incubated directly with 1,25-(OH) 2 D 3 or 24,25-(OH) 2 D 3 show that these organbility (Kyeyune-Nyombi et al, 1991). More recently, a second pathway that operates independently of the elles are regulated directly by the metabolites in a cell maturation-dependent manner (Schwartz et al, 1988b; VDR has emerged. 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 have been shown to act directly on the plasma mem- Swain et al, 1993;Boyan et al, 1994b;.…”

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confidence: 99%

“…1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 have been shown to act directly on the plasma mem- Swain et al, 1993;Boyan et al, 1994b;. The results of these latter studies are unequivobrane of target cells, causing rapid changes in calcium flux (Langston et al, 1990;Farach-Carson et al, 1991; cable support for the nongenomic action of vitamin D metabolites, because matrix vesicles contain no DNA Zhou et al, 1992;Yukihiro et al, 1994), fatty acid metabolism (Matsumoto et al, 1981;Rasmussen et al, or RNA and, therefore, no possibility of genomic control over the response (Schwartz et al, 1988b;Swain et 1982;Schwartz et al, 1990Schwartz et al, , 1992b, phospholipid metabolism (Tang et al, 1987;Lieberherr al., 1993;Boyan et al, 1994b;. The existence of this mechanism of regulatory control, at et al ., 1989;Bourdeau et al, 1990;Wali et al, 1990), membrane fluidity (Swain et al, 1993), and protein the membrane, is further supported by the recent reports of others demonstrating non-nuclear actions of kinase C activity (Sylvia et al, 1993.…”

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confidence: 99%

“…By use of a cartilage cell culture and nongenomic pathways are involved in 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 action. 1,25-(OH) 2 D 3 has a model in which chondrocytes from resting zone (reserve zone) and growth zone (prehypertrophic and upper hy-rapid effect on PKC activity in the cell layer of growth zone chondrocytes that does not require new gene tranpertrophic zones) cartilage are isolated and placed into culture (Boyan et al, 1988b), we have been able to scription or protein synthesis (Sylvia et al, 1993). In contrast, 24,25-(OH) 2 D 3 stimulates PKC activity in examine the role of cell maturation in response to various factors.…”

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A-ring analogues of 1,25-(OH)2D3 with low affinity for the vitamin D receptor modulate chondrocytes via membrane effects that are dependent on cell maturation

Greising

Schwartz²,

Posner

et al. 1997

J. Cell. Physiol.

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1,25-(OH)2D3 (1,25) and 24,25-(OH)2D3(24,25) mediate their effects on chondrocytes through the classic vitamin D receptor (VDR) as well as through rapid membrane-mediated mechanisms, which result in both nongenomic and genomic effects. In intact cells, it is difficult to distinguish between genomic responses via the VDR and genomic and nongenomic responses via membrane-mediated pathways. In this study, we used two analogues of 1,25 that have been modified on the A-ring (2a, 2b) and are only 0.1% as effective in binding to the VDR as 1,25, to examine the role of the VDR in the response of rat costochondral resting zone (RC) and growth zone (GC) chondrocytes to 1,25 and 24,25. Chondrocyte proliferation ([3H]-thymidine incorporation), proteoglycan production ([35S]-sulfate incorporation), and second messenger activation (activity of protein kinase C) were measured after treatment with 10(-8) M 1,25, 10(-7) M 24,25, or the analogues at 10(-9)-10(-6) M. Both analogues inhibited proliferation of both cell types, as did 1,25 and 24,25. Neither 2a nor 2b had an effect on proteoglycan production by GCs or RCs. 2a caused a dose-dependent stimulation of protein kinase C (PKC) that was not inhibited by cycloheximide or actinomycin D in either GC or RC cells. 2b, on the other hand, had no effect on PKC activity in RCs and only a slight stimulatory effect in GCs. Both cells produce matrix vesicles, extracellular organelles associated with the initial stages of calcification, in culture that are regulated by vitamin D metabolites. Since these organelles contain no DNA or RNA, they provide an excellent model for studying the mechanisms used by vitamin D metabolites to mediate their nongenomic effects. When matrix vesicles were isolated from naive cultures of growth zone cells and treated with 2a, a dose-dependent inhibition of PKC activity was observed that was similar to that found with 1,25-(OH)2D3. Plasma membranes contained increased PKC activity after treatment with 2a, but the magnitude of the effect was less than that seen with 1,25-(OH)2D3. Analogue 2b had no affect on PKC activity in either membrane fraction. When matrix vesicles from resting zone chondrocyte cultures were treated with 24,25-(OH)2D3, a significant decrease in PKC activity was observed. No change in enzyme activity was found for either 1,25-(OH)2D3 or the analogues. PKC activity in the plasma membrane fraction, however, was increased by 24,25-(OH)2D3 as well as by analogue 2a. This study shows that these analogues, with little or no binding to the vitamin D receptor, can affect cell proliferation and PKC activity, but not proteoglycan production. The direct membrane effect is analogue specific and cell maturation dependent. Further, by eliminating the VDR-mediated component of the cellular response, we have provided further evidence for the existence of a membrane receptor(s) involved in mediating nongenomic effects of vitamin D metabolites.

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Section: Synthesis Of Vitamin D Analoguesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A-ring analogues of 1,25-(OH)2D3 with low affinity for the vitamin D receptor modulate chondrocytes via membrane effects that are dependent on cell maturation

Greising

Schwartz²,

Posner

et al. 1997

J. Cell. Physiol.

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“…This may not be the case for matrix vesicles, however. Matrix vesicles possess an active phospholipid metabolism that is regulated independently from that of the cell (28). Their phospholipid composition is distinct from that of the plasma membrane as well (29 -31).…”

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confidence: 99%

1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

Schwartz

Sylvia

Larsson

et al. 2002

Journal of Biological Chemistry

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Matrix vesicles are extracellular organelles involved in mineral formation that are regulated by 1␣,25 (OH) 2 D 3 . Prior studies have shown that protein kinase C (PKC) activity is involved in mediating the effects of 1␣,25(OH) 2 D 3 in both matrix vesicles and plasma membranes. Here, we examined the regulation of matrix vesicle PKC by 1␣,25(OH) 2 D 3 during biogenesis and after deposition in the matrix. When growth zone costochondral chondrocytes were treated for 9 min with 1␣,25 (OH) 2 D 3 , PKC in matrix vesicles was inhibited, while PKC␣ in plasma membranes was increased. In contrast, after treatment for 12 or 24 h, PKC in matrix vesicles was increased, while PKC␣ in plasma membranes was unchanged. The effect of 1␣,25(OH) 2 D 3 was stereospecific and metabolite-specific. Monensin blocked the increase in matrix vesicle PKC after 24 h, suggesting the secosteroid-regulated packaging of PKC. In addition, the 1␣,25(OH) 2 D 3 membrane vitamin D receptor (1,25-mVDR) was involved, since a specific antibody blocked the 1␣,25(OH) 2 D 3 -dependent changes in PKC after both long and short treatment times. In contrast, antibodies to annexin II had no effect, and there was no evidence for the presence of the nuclear VDR on Western blots. To investigate the signaling pathways involved in regulating matrix vesicle PKC activity after biosynthesis, matrix vesicles were isolated and then treated for 9 min with 1␣,25(OH) 2 D 3 in the presence and absence of specific inhibitors. Inhibition of phosphatidylinositol-phospholipase C, phospholipase D, or G i /G s had no effect. However, inhibition of G q blocked the effect of 1␣,25(OH) 2 D 3 . The rapid effect of 1␣,25(OH) 2 D 3 also involved the 1,25-mVDR. Moreover, arachidonic acid was found to stimulate PKC when added directly to isolated matrix vesicles. These results indicate that matrix vesicle PKC is regulated by 1␣,25(OH) 2 D 3 at three levels: 1) during matrix vesicle biogenesis; 2) through direct action on the membrane; and 3) through production of other factors such as arachidonic acid.Costochondral growth plate chondrocytes metabolize 25 (OH)D 3 in a regulated manner, producing and secreting 1,25 (OH) 2 D 3 and 24,25(OH) 2 D 3 (1, 2). The physiological importance of this is not yet well understood. 1␣,25(OH) 2 D 3 exerts direct effects on matrix vesicles isolated from the extracellular matrix of growth plate chondrocytes (3), suggesting that the cells may use local production of the vitamin D metabolite as a mechanism for controlling events in the matrix. A number of observations support this hypothesis. Treatment of matrix vesicles with 1␣,25(OH) 2 D 3 causes increased alkaline phosphatase specific activity, which is associated with the onset of calcification (4). In addition, phospholipase A 2 (PLA 2 ) 1 specific activity is increased (5), which may lead to a loss of membrane integrity and the release of proteinases capable of remodeling the matrix (6, 7). One of the matrix metalloproteinases that are present in matrix vesicles, stromelysin-1 (MMP-3), has been shown to ...

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Direct Effect of Vitamin D Metabolites on Matrix Vesicle Alkaline Phosphatase

Cited by 2 publications

References 5 publications

A-ring analogues of 1,25-(OH)2D3 with low affinity for the vitamin D receptor modulate chondrocytes via membrane effects that are dependent on cell maturation

A-ring analogues of 1,25-(OH)2D3 with low affinity for the vitamin D receptor modulate chondrocytes via membrane effects that are dependent on cell maturation

1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

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