title: Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast--comparison to its effects on osteoarthritic chondrocytes.
abstract: OBJECTIVE
  Synoviocytes play a crucial role in the inflammatory response leading to structural damage in OA. Our aim was to assess the effects of diacerein and NSAIDs on cellular responses of synoviocytes associated with inflammation and structural integrity of cartilage in OA.
  
  
  METHODS
  The effects of diacerein, celecoxib, diclofenac, meloxicam and indomethacin on prostaglandin (PG) E2 production, cyclo-oxygenase-2 (COX-2) protein expression, nitrite levels, presence of MMP-1 and -13, and activation of nuclear factor-kappaB (NF-kappaB) were studied on stimulated OA synoviocytes and chondrocytes.
  
  
  RESULTS
  Diacerein and NSAIDs inhibited IL-1beta-stimulated NF-kappaB activation in synoviocytes and chondrocytes except indomethacin in synoviocytes. Diacerein further increased COX-2 protein expression and PGE2 synthesis in synoviocytes stimulated with IL-1beta, while no effect was observed on stimulated chondrocytes. NSAIDs diminished until almost basal levels PGE2 release in both cells and, surprisingly, these drugs also diminished COX-2 protein expression both in synoviocytes and chondrocytes. With regard to structural mediators, diacerein decreased MMP-13 levels in synoviocytes but did not modify MMP-1 presence. NSAIDs induced a significant increase in MMP-1 levels in both cell types and in MMP-13 levels in chondrocytes.
  
  
  CONCLUSIONS
  Diacerein does not seem to reduce but rather increase inflammatory mediators in synoviocytes, while it does not overall affect chondrocyte inflammatory profile.
authors: Joint and Bone Research Unit, Rheumatology Department, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors: M A
authors: MA
authors: Alvarez-Soria
authors: G
authors: G
authors: Herrero-Beaumont
authors: O
authors: O
authors: Sánchez-Pernaute
authors: M
authors: M
authors: Bellido
authors: R
authors: R
authors: Largo
mesh_terms: D000880:Anthraquinones / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002358:Cartilage, Articular; D002478:Cells, Cultured; D019902:Chondrocytes / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D007719:Knee Joint; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000032:analysis / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D016328:NF-kappa B; D009573:Nitrites; C025292:diacerein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone