Prostaglandin E2 and prostaglandin F2α differentially modulate matrix metabolism of human nucleus pulposus cells.
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.
Vo
Nam V
NV
Ferguson Laboratory for Orthopaedic Research, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania, USA. von@upmc.edu
Sowa
Gwendolyn A
GA
Kang
James D
JD
Seidel
Christopher
C
Studer
Rebecca K
RK
D000328:Adult; D053674:Aggrecans / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism* / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053675:Versicans / Q000378:metabolism
D053674:Aggrecans; D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D024043:Collagen Type II; D019715:Tissue Inhibitor of Metalloproteinase-1; D053675:Versicans; D016718:Arachidonic Acid; D015237:Dinoprost; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone