PMID- 11950021
OWN - NLM
STAT- MEDLINE
DCOM- 20021004
LR  - 20181130
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 29
IP  - 4
DP  - 2002 Apr
TI  - Metabolism of human articular chondrocytes cultured in alginate beads. Longterm 
      effects of interleukin 1beta and nonsteroidal antiinflammatory drugs.
PG  - 772-82
AB  - OBJECTIVES: To investigate the longterm effects (12 days) of nonsteroidal 
      antiinflammatory drugs [NSAID: aceclofenac (ACECLO), sodium diclofenac (DICLO), 
      indomethacin (INDO), nimesulide (NIM), rofecoxib (ROFE), celecoxib (CELE), 
      piroxicam (PIROX), and ibuprofen (IBUP)] on the metabolism of human chondrocytes 
      cultured in alginate beads. METHODS: Enzymatically isolated osteoarthritic (OA) 
      chondrocytes were cultured in alginate beads in a well defined culture medium for 
      12 days. The DNA content was measured according to a fluorimetric method and cell 
      proliferation was determined by the incorporation of 3H-thymidine in the newly 
      synthesized DNA. Interleukin 6 (IL-6) and IL-8, stromelysin [matrix 
      metalloproteinase-3 (MMP-3)], and aggrecan (AGG) production were assayed by 
      specific enzyme amplified sensitivity immunoassays, and prostaglandin E2 (PGE2) 
      production by specific radioimmunoassay. All NSAID were tested at the mean peak 
      plasma concentration (Cmax) obtained after oral administration of a therapeutic 
      dose. RESULTS: In alginate beads, chondrocytes synthesized high amounts of AGG, 
      which were largely (98%) immobilized in the alginate matrix. A large amount (43%) 
      of the IL-8 produced was stored in the alginate beads, whereas almost all IL-6 
      production (94%) was released in the culture supernatant. At the therapeutic 
      concentration, all NSAID tested fully blocked PGE2 production. ACECLO, DICLO, 
      INDO, NIM significantly inhibited basal and IL-1beta stimulated IL-6 production; 
      CELE and IBUP only inhibited IL-1beta stimulated IL-6 production; and ROFE and 
      PIROX had no significant effects. No NSAID showed significant effects on basal 
      and IL-1beta stimulated IL-8 production, except CELE and IBUP, which slightly 
      increased basal IL-8 production. ACECLO and INDO increased AGG content by 25% in 
      the alginate beads, while the other NSAID were without significant effect. No 
      NSAID were able to modify the inhibitory effect of IL-1beta on AGG production. 
      NSAID did not modify MMP-3 production. CONCLUSION: The mechanism of action of 
      NSAID seems to be multifactorial and not limited to the inhibition of 
      cyclooxygenases. Further, in our culture conditions, at the Cmax and by 
      comparison with other NSAID, ACECLO and INDO show an advantageous activity 
      profile. They fully blocked PGE2 production, inhibited IL-6 synthesis, and 
      increased aggrecan synthesis. These effects appear advantageous for the longterm 
      treatment of chronic joint diseases such as osteoarthritis.
FAU - Sanchez, Christelle
AU  - Sanchez C
AD  - Bone and Cartilage Metabolism Research Unit, University Hospital, CHU 
      Sart-Tilman, Liege, Belgium.
FAU - Mateus, Marguarida M
AU  - Mateus MM
FAU - Defresne, Marie-Paule
AU  - Defresne MP
FAU - Crielaard, Jean-Michel R
AU  - Crielaard JM
FAU - Reginster, Jean-Yves L
AU  - Reginster JY
FAU - Henrotin, Yves E
AU  - Henrotin YE
LA  - eng
PT  - Journal Article
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Aggrecans)
RN  - 0 (Alginates)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Hexuronic Acids)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Proteoglycans)
RN  - 8A5D83Q4RW (Glucuronic Acid)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Aggrecans
MH  - Alginates
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Cadaver
MH  - Cartilage, Articular/drug effects/*metabolism/pathology
MH  - Cell Culture Techniques/methods
MH  - Cell Division
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/*metabolism/pathology
MH  - DNA/biosynthesis
MH  - *Extracellular Matrix Proteins
MH  - Glucuronic Acid
MH  - Hexuronic Acids
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Lectins, C-Type
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Osteoarthritis/metabolism/pathology
MH  - Proteoglycans/metabolism
EDAT- 2002/04/13 10:00
MHDA- 2002/10/09 04:00
CRDT- 2002/04/13 10:00
PHST- 2002/04/13 10:00 [pubmed]
PHST- 2002/10/09 04:00 [medline]
PHST- 2002/04/13 10:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 2002 Apr;29(4):772-82.