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 (NSAI Ds) are frequently used to block PG production to treat back pain. Hence this study aimed to (1) quantify gene expression of arachiclonic 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 F2 alpha (PGF(2 alpha)), resulting in elevated PGE(2) and PGF(2 alpha) production in conditioned mocha of disc cells PGE(2) diminished disc cell proteoglycan synthesis, in a dose-dependent manner Semiquantitative RT-PGR revealed differential effects of PGE(2) and PGF(2 alpha) on disc cell expression of key matrix structural genes. aggrecan, versican, collagens type I and II PGE(2) and PGF(2 alpha) also decreased message for the anabolic factor, IGF-1 PGE2 decreased mRNA expression for the anti-catabolic factor TIMP-1 while PGF(2 alpha) increased mRNAs for catabolic factors MMP-1 and MMP-3 Thus, PGE(2) and PGF(2 alpha) may have an overall negative impact on disc matrix homeostasis, and the use of NSAIDs may impact disc metabolism is well as treat back pain (C) 2010 Orthopaedic Research Society Published by Wiley Periodicals, Inc J Orthop Res 28 1259-1266, 2010