Mechanisms regulating differential activation of membrane-mediated signaling by 1α,25(OH)2D3 and 24R,25(OH) 2D3

B. D. Boyan, E. G. Jennings, L. Wang, Z. Schwartz

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Vitamin D metabolites 1α,25(OH)2D3 and 24R,25(OH)2D3 regulate endochondral ossification in a cell maturation-dependent manner via membrane-mediated mechanisms. 24R,25(OH) 2D3 stimulates PKC activity in chondrocytes from the growth plate resting zone, whereas 1α,25(OH)2D3 stimulates PKC in growth zone chondrocytes. We used the rat costochondral growth plate cartilage cell model to study how these responses are differentially regulated. 1α,25(OH)2D3 acts on PKC, MAP kinase, and downstream physiological responses via phosphatidylinositol-specific PLC-β; 24R,25(OH)2D3 acts via PLD. In both cases, diacylglycerol (DAG) is increased, activating PKC. Both cell types possess membrane and nuclear receptors for 1α,25(OH)2D3, but the mechanims that render the 1α,25(OH)2D3 pathway silent in resting zone cells or the 24R,25(OH)2D3 pathway silent in growth zone cells are unclear. PLA2 is pivotal in this process. 1α,25(OH)2D3 stimulates PLA2 activity in growth zone cells and 24R,25(OH)2D3 inhibits PLA2 activity in resting zone cells. Both processes result in PKC activation. To understand how negative regulation of PLA2 results in increased PKC activity in resting zone cells, we used PLA2 activating peptide to stimulate PLA2 activity and examined cell response. PLAP is not expressed in resting zone cells in vivo, supporting the hypothesis that PLA2 activation is inhibitory to 24R,25(OH)2D3 action in these cells.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume89-90
DOIs
StatePublished - May 2004

Keywords

  • 1α,25(OH)D
  • 24R,25(OH)D
  • Chondrocytes
  • Phospholipase A
  • Phospholipase A activating protein (PLAP)
  • Phospholipase C (PLC)
  • Protein kinase C (PKC)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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