title: Effects of celecoxib on human chondrocytes--enhanced production of chemokines.
abstract: OBJECTIVE
  The purpose of this study was to examine the effects of a selective cyclooxigenase-2 (COX-2) inhibitor (celecoxib) comparing diclofenac.
  
  
  METHODS
  Using chondrocytes derived from cartilage of non-arthritic (NA) subjects or patients with osteoarthritis (OA) or rheumatoid arthritis (RA), we examined the effects of celecoxib on incorporation of 3H-thymidine and 35S-sulfate, apoptosis, and production of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and regulated upon activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1a and nitric oxide (NO).
  
  
  RESULTS
  Celecoxib and diclofenac tended to reduce 3H-tymidine incorporation of chondrocytes. Celecoxib induced apoptosis in a dose-dependent manner, but to a lesser degree than diclofenac. Celecoxib inhibited proteoglycan synthesis (indicated by 35S-sulfate incorporation) in NA chondrocytes, but not in OA and RA chondrocytes. Celecoxib increased interleukin-1 (IL-1)-induced production of RANTES and MIP-1alpha by chondrocytes and decreased IL-1-induced NO production by chondrocytes, whereas it did not affect MMP production.
  
  
  CONCLUSIONS
  Celecoxib had both beneficial and adverse effects on chondrocytes. RA, OA and NA chondrocytes showed different responses. Interestingly, celecoxib enhanced the production of chemokines.
authors.affiliation: Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan. Nakamura@nms.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Masuko
authors.forename: K
authors.initials: K
authors.lastname: Yudoh
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068579:Celecoxib; D002478:Cells, Cultured; D054405:Chemokine CCL3; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D009569:Nitric Oxide; D053505:Matrix Metalloproteinases, Secreted; D000068579:Celecoxib