[Effect of diacerhein (ART 50) on the matrix synthesis and collagenase secretion by cultured joint chondrocytes in rabbits].
Cultured rabbit joint chondrocytes were exposed to diacerhein (DAR : ART 50, Negma, 10(-6) to 10(-4) M), which has proved effective and safe when given for two months for the treatment of osteoarthritis. Experiments were performed with and without 500 pg/ml human recombinant interleukin-1 to determine whether diacerhein antagonizes the effects of this monokine. Glycosaminoglycan production was measured by 35S-sulfate incorporation followed by cetylpyridinium precipitation, collagen production by 3H-proline labeling and bacterial collagenase digestion, and collagenase production by determination of the amount of 3H-collagen that underwent degradation. Incubation of chondrocytes with diacerhein for 24 hours was not associated with substantial changes in glycosaminoglycan or collagen production but substantially antagonized interleukin-1-mediated enhancement of collagenase production. With longer incubation periods (6 days) with the 10(-6) M concentration of diacerhein, production of glycosaminoglycans and collagen increased. Incubation with both diacerhein and interleukin-1 for six days partly antagonized the cytokine's inhibitory effect on glycosaminoglycan and collagen production. During these experiments, the medium's ability to break down collagen was consistently reduced by diacerhein, even in the presence of interleukin-1. These data demonstrate that diacerhein can reduce or even abolish interleukin-1-mediated enhancement of collagenase production by joint chondrocytes. This effect may lead to less erosion of cartilage in degenerative joint diseases.
Boittin
M
M
Laboratoire de Biochimie du Tissu Conjonctif, CHU Côte de Nacre, Caen, Paris.
Rédini
F
F
Loyau
G
G
Pujol
J P
JP
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology* / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011509:Proteoglycans; C025292:diacerein; D017364:Collagenases
Effet de la diacerhéine (ART 50) sur la synthèse de la matrice et la sécrétion de collagénase par des chondrocytes articulaires de lapin en culture.