Effects of dexamethasone on proteoglycan content and gene expression of IL-1beta-stimulated osteoarthrotic chondrocytes in vitro.
We studied the effects of dexamethasone on proteoglycan (PG) concentration and gene expression in human osteoarthrotic chondrocytes stimulated with IL-1beta. Cartilage samples were taken from 7 patients with osteoarthrosis of the knee and chondrocytes cultivated in alginate beads. Dexamethasone was added in three concentrations (10(-5), 10(-6), 10(-7) M) to IL-1beta (100 pg/nL)-stimulated chondrocytes. PG concentration was estimated by a dimethylmethylene blue assay. To assess cell proliferation, DNA content was measured fluorometrically. Quantitative Lightcycler-PCR was used to estimate the mRNA levels of stromelysin-1 (MMP-3) and aggrecan (AGG). The proliferation rate was unchanged in all treatment groups. IL-1beta increased MMP-3 expression by 44% and inhibited AGG expression by 16%, but PG-concentration was reduced by 7%. The addition of dexamethasone to IL-1beta-stimulated chondrocytes further reduced the PG concentration by 19% at 10(-5) M and by 17% at 10(-7) M. The MMP-3 expression was inhibited between 27-53% and the AGG expression between 30-46% by dexamethasone. In osteoarthrotic chondrocytes, dexamethasone in an appropriate dose range reduced the expression of MMP-3 and AGG at the same time. The resulting decrease in PG concentration should be considered when using intraarticular corticosteroids to treat an osteoarthrotic joint.
Stöve
Johannes
J
Department of Orthopaedic Surgery, University of Heidelberg, Mannheim, Germany.
Schöniger
Ralf
R
Huch
Klaus
K
Brenner
Rolf
R
Günther
Klaus-Peter
KP
Puhl
Wolfhart
W
Scharf
Hanns-Peter
HP
D000368:Aged; D053674:Aggrecans; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019902:Chondrocytes / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007719:Knee Joint / Q000187:drug effects / Q000601:surgery; D037181:Lectins, C-Type; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000187:drug effects; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000601:surgery*; D011509:Proteoglycans / Q000032:analysis* / Q000187:drug effects*; D013268:Stimulation, Chemical
D053674:Aggrecans; D000893:Anti-Inflammatory Agents; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D037181:Lectins, C-Type; D011509:Proteoglycans; D003907:Dexamethasone; D019278:Matrix Metalloproteinase 3