1,25-(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism that involves changes in phospholipid metabolism and the action of arachidonic acid and PGE2

Boyan, Barbara D.; Sylvia, V. L.; Dean, David D.; Pedrozo, H. A.; Toro, F. Del; Nemere, Ilka; Posner, Gary H.; Schwartz, Zvi

doi:10.1016/s0039-128x(98)00099-3

Cited by 83 publications

(35 citation statements)

References 57 publications

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“…In growth zone chondrocytes, 1␣,25(OH) 2 D 3 (10 nM) causes a rapid increase in PKC activity that was insensitive to actinomycin D and cycloheximide (67,473). A recent study showed that the activation of PKC by 1␣,25(OH) 2 affected PLD in growth zone cells.…”

Section: G Vitamin Dmentioning

confidence: 99%

Nongenomic Steroid Action: Controversies, Questions, and Answers

Lösel

Falkenstein

Feuring

et al. 2003

Physiological Reviews

503

321

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Lösel, Ralf M., Elisabeth Falkenstein, Martin Feuring, Armin Schultz, Hanns-Christian Tillmann, Karin Rossol-Haseroth, and Martin Wehling. Nongenomic Steroid Action: Controversies, Questions, and Answers. Physiol Rev 83: 965–1016, 2003; 10.1152/physrev.00003.2003.—Steroids may exert their action in living cells by several ways: 1) the well-known genomic pathway, involving hormone binding to cytosolic (classic) receptors and subsequent modulation of gene expression followed by protein synthesis. 2) Alternatively, pathways are operating that do not act on the genome, therefore indicating nongenomic action. Although it is comparatively easy to confirm the nongenomic nature of a particular phenomenon observed, e.g., by using inhibitors of transcription or translation, considerable controversy exists about the identity of receptors that mediate these responses. Many different approaches have been employed to answer this question, including pharmacology, knock-out animals, and numerous biochemical studies. Evidence is presented for and against both the participation of classic receptors, or proteins closely related to them, as well as for the involvement of yet poorly understood, novel membrane steroid receptors. In addition, clinical implications for a wide array of nongenomic steroid actions are outlined.

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Section: G Vitamin Dmentioning

confidence: 99%

Nongenomic Steroid Action: Controversies, Questions, and Answers

Lösel

Falkenstein

Feuring

et al. 2003

Physiological Reviews

503

321

View full text Add to dashboard Cite

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“…Whether this is also the case for growth zone cells is not known, however. PKC is regulated by 24R,25(OH) 2 D 3 in resting zone cells, but 1␣,25(OH) 2 D 3 regulates activity in growth zone cells, and these two metabolites use two distinctly different mechanisms to regulate PKC activity in their target cells (9,21). Moreover, matrix vesicle composition, including phospholipids and enzyme activities, and regulation of matrix vesicle function differs between the two cell types (see Refs.…”

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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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“…While the recent observations on rapid 1,25(OH) 2 D signalling are interesting, the central importance of VDRmediated signalling appears to leave little room for an independent effect of these pathways. To date, the area that best demonstrates the importance of the rapid activation of kinase pathways by 1,25(OH) 2 D is the modulation of growth-zone chondrocyte biology (Boyan et al 1994(Boyan et al , 1999(Boyan et al , 2003. Treatment of growth-zone chondrocytes with 1,25(OH) 2 D activates phospholipase A 2 and causes an increase in membrane fluidity, activates phospholipase C leading to the activation of protein kinase C and release of intracellular Ca, and indirectly activates protein kinase A through production of prostaglandin E 2 .…”

Section: The Two Modes Of 125 Dihydroxyvitamin D Actionmentioning

confidence: 99%

Reshaping the way we view vitamin D signalling and the role of vitamin D in health

2004

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Although the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH) 2 D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH) 2 D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH) 2 D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

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1,25-(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism that involves changes in phospholipid metabolism and the action of arachidonic acid and PGE2

Cited by 83 publications

References 57 publications

Nongenomic Steroid Action: Controversies, Questions, and Answers

Nongenomic Steroid Action: Controversies, Questions, and Answers

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

Reshaping the way we view vitamin D signalling and the role of vitamin D in health

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