Effects of diacerein on biosynthesis activities of chondrocytes in culture.
The maintenance of articular cartilage integrity requires a balance between anabolic and catabolic processes which are under the control of chondrocytes. These cells are living in an anaerobic environment and normally do not divide. They are responsible for the continuous maintenance of the cartilage extracellular matrix (ECM). Although multiple factors are involved in the dynamic homeostasis of cartilage, increases in cytokines such as interleukin-1 (IL-1) are associated with a decrease in synthesis and an increase in degradation of the proteoglycans and collagens. Conversely, growth factors such as transforming growth factor-beta (TGF-beta) stimulate chondrocyte synthesis of collagens and proteoglycans, and reduce the activity of IL-1 stimulated metalloproteases, thus opposing the inhibitory and catabolic effects of IL-1. By its capability to reduce IL-1 effects and to stimulate TGF-beta expression in cultured articular chondrocytes, diacerein could favour anabolic processes in the OA cartilage and, hence may contribute to delay the progression of the disease.
Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, Caen, France.
J P
JP
Pujol
N
N
Felisaz
K
K
Boumediene
C
C
Ghayor
J F
JF
Herrouin
P
P
Bogdanowicz
P
P
Galera
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013268:Stimulation, Chemical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; C025292:diacerein