title: Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage.
abstract: OBJECTIVE
  Peroxisome proliferator activated receptor α (PPARα) agonists are used in clinical practice as lipid-lowering drugs and are also known to exert anti-inflammatory effects on various tissues. We hypothesized that PPARα activation leads to anti-inflammatory and anti-destructive effects in human OA cartilage.
  
  
  METHODS
  Cartilage explants obtained from six OA patients were cultured for 48 h with 10 ng/ml interleukin (IL)1β as a pro-inflammatory stimulus. 100 μM Wy-14643, a potent and selective PPARα agonist, was added to the cultures and gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, collagen type II (COL2A1), aggrecan and PPARα in cartilage explants and the release of glycosaminoglycans (GAGs), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in the culture media were analyzed and compared to the control without Wy-14643.
  
  
  RESULTS
  Addition of Wy-14643 decreased mRNA expression of MMP1, MMP3 and MMP13 in cartilage explants that responded to IL1β, whereas Wy-14643 did not affect gene expression of COL2A1 and aggrecan. Wy-14643 also decreased secretion of inflammatory marker NO in the culture medium of cartilage explants responding to IL1β. Wy-14643 inhibited the release of GAGs by cartilage explants in culture media.
  
  
  CONCLUSIONS
  PPARα agonist Wy-14643 inhibited the inflammatory and destructive responses in human OA cartilage explants and did not have an effect on COL2A1 or aggrecan mRNA expression. These effects of PPARα agonists on osteoarthritic cartilage warrant further investigation of these drugs as a potential therapeutic strategy for osteoarthritis (OA).
authors: Department of Orthopaedic Surgery and Traumatology, University of Antwerp, Belgium.
authors: S
authors: S
authors: Clockaerts
authors: Y M
authors: YM
authors: Bastiaansen-Jenniskens
authors: C
authors: C
authors: Feijt
authors: J A N
authors: JA
authors: Verhaar
authors: J
authors: J
authors: Somville
authors: L S
authors: LS
authors: De Clerck
authors: G J V M
authors: GJ
authors: Van Osch
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D006025:Glycosaminoglycans; D047493:PPAR alpha; D011743:Pyrimidines; D009569:Nitric Oxide; C006253:pirinixic acid; D020782:Matrix Metalloproteinases; D015232:Dinoprostone