Plasma membrane requirements for 1α,25(OH)2D3 dependent PKC signaling in chondrocytes and osteoblasts

Barbara D. Boyan, Liping Wang, Kevin L. Wong, Hanjoong Jo, Zvi Schwartz

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

1,25-Dihydroxyvitamin D3 [1α,25(OH)2D 3] acts on chondrocytes and osteoblasts through traditional nuclear Vitamin D receptor (VDR) mechanisms as well as through rapid actions on plasma membranes that initiate intracellular signaling pathways. We have investigated the mechanisms involved in activation of protein kinase C (PKC) and downstream biological responses that depend on the latter pathway. These studies show that PKC activation depends on presence of a membrane receptor ERp60 and rapid increases in phospholipase A2 (PLA2) activity. Cells that are responsive to 1α,25(OH)2D3 express PLA 2 activating protein (PLAA), suggesting a link between ERp60 and PLA2. Increased PLA2 results in increased arachidonic acid release and formation of lysophospholipid, which then activates phospholipase C beta (PLCβ), leading to rapid formation of inositol-trisphosphate (IP3) and diacylglycerol (DAG). PLA2, PLC, and DAG are all associated with lipid rafts including caveolae in many cells, suggesting that the caveolar environment may be an important mediator of PKC activation by 1α,25(OH)2D3. Here, we use the VDR-/- mouse costochondral cartilage growth plate to examine the expression of ERp60 and PLAA in vivo in 1α,25(OH)2D3-responsive hypertrophic chondrocytes (growth zone cells) and in resting zone cells that do not respond to this Vitamin D metabolite in vitro. In addition, we determined if intact lipid rafts are required for the response of rat costochondral cartilage growth zone cells to 1α,25(OH)2D3. The results show that ERp60 and PLAA are localized to 1α,25(OH)2D 3-responsive growth zone cells and metaphyseal osteoblasts, even in VDR-/- mice. Disruption of lipid rafts using beta-cyclodextrin blocks the activation of PKC by 1α,25(OH)2D3 and reduces the ability of 1α,25(OH)2D3 to regulate [ 35S]-sulfate incorporation.

Original languageEnglish (US)
Pages (from-to)286-290
Number of pages5
JournalSteroids
Volume71
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • 1α,25(OH)D
  • Caveolae
  • Chondrocytes
  • ERp60
  • Osteoblasts
  • PLAA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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