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Prostaglandin E2 and prostaglandin F2α differentially modulate matrix metabolism of human nucleus pulposus cells.

Abstract
Prostaglandin (PG) actions on disc metabolism are unclear even though certain PGs are highly expressed by disc cells under inflammatory conditions and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to block PG production to treat back pain. Hence this study aimed to (1) quantify gene expression of arachidonic acid cascade components responsible for PG synthesis and (2) examine the effects of key PGs on disc matrix homeostasis. Microarray analysis revealed that inflammatory stress increases expression of synthases and receptors for prostaglandin E2 (PGE(2)) and prostaglandin F2α (PGF(2α)), resulting in elevated PGE(2) and PGF(2α) production in conditioned media of disc cells. PGE(2) diminished disc cell proteoglycan synthesis, in a dose-dependent manner. Semiquantitative RT-PCR revealed differential effects of PGE(2) and PGF(2α) on disc cell expression of key matrix structural genes, aggrecan, versican, collagens type I and II. PGE(2) and PGF(2α) also decreased message for the anabolic factor, IGF-1. PGE(2) decreased mRNA expression for the anti-catabolic factor TIMP-1 while PGF(2α) increased mRNAs for catabolic factors MMP-1 and MMP-3. Thus, PGE(2) and PGF(2α) may have an overall negative impact on disc matrix homeostasis, and the use of NSAIDs may impact disc metabolism as well as treat back pain.
AuthorsNam V Vo, Gwendolyn A Sowa, James D Kang, Christopher Seidel, Rebecca K Studer
JournalJournal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 28 Issue 10 Pg. 1259-66 (Oct 2010) ISSN: 1554-527X [Electronic] United States
PMID20839316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
CopyrightPublished by Wiley Periodicals, Inc. J Orthop Res 28:1259-1266, 2010.
Chemical References
  • Aggrecans
  • Anti-Inflammatory Agents, Non-Steroidal
  • Collagen Type I
  • Collagen Type II
  • Tissue Inhibitor of Metalloproteinase-1
  • Versicans
  • Arachidonic Acid
  • Dinoprost
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1
  • Dinoprostone
Topics
  • Adult
  • Aggrecans (metabolism)
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Arachidonic Acid (metabolism)
  • Cells, Cultured
  • Collagen Type I (metabolism)
  • Collagen Type II (metabolism)
  • Dinoprost (metabolism, pharmacology)
  • Dinoprostone (metabolism, pharmacology)
  • Humans
  • Intervertebral Disc (cytology, drug effects, metabolism)
  • Matrix Metalloproteinase 1 (metabolism)
  • Matrix Metalloproteinase 3 (metabolism)
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-1 (metabolism)
  • Versicans (metabolism)

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