Rhein, the metabolite of diacerhein, reduces the proliferation of osteoarthritic chondrocytes and synoviocytes without inducing apoptosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scandinavian Journal of Rheumatology Année : 2009

Rhein, the metabolite of diacerhein, reduces the proliferation of osteoarthritic chondrocytes and synoviocytes without inducing apoptosis

Résumé

Objective: The aim of this study was to determine the effects of pharmacologically relevant concentrations of rhein (1,8‐dihydroxy‐3‐carboxyanthraquinone) on the cell proliferation rate of human chondrocytes and synoviocytes. Methods: Cultures of human osteoarthritic synoviocytes and chondrocytes were incubated with 10−6, 10−5, and 10−4 M rhein. [3H]thymidine incorporation was used to determine rhein proliferative effects after incubation periods of 24 h, 48 h, and 1 week. The cytotoxicity of the drug was assayed with a nonradioactive assay kit. Nuclear extracts were used to detect variations in cell‐cycle proteins (p21, p27, and cyclin D1) by Western blotting. The effect of rhein on apoptosis was investigated by measurement of caspase‐3/7 activity and DNA fragmentation. Results: Rhein was found to downregulate the proliferation rate of both chondrocytes and synoviocytes, two‐fold for 10−5 M rhein and five‐ to six‐fold for 10−4 M rhein. No cytotoxicity of the drug was observed. Rhein (10−4 M) decreased caspase‐3/7 activity and did not induce DNA fragmentation. Western blots showed that 10−4 M rhein increased the expression of p21 and/or p27, but not that of cyclin D1. Conclusions: Rhein has previously been shown to reduce the interleukin (IL)‐1β deleterious effects on osteoarthritis (OA) cartilage through inhibition of the expression of degrading enzymes. Here, rhein was also found to inhibit proliferation of both synoviocytes and chondrocytes, suggesting that the drug may decrease the development of the inflammatory synovial tissue that accompanies joint pathologies. Both its anti‐catabolic and anti‐proliferative effects may explain its beneficial effect in the treatment of joint diseases.
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hal-04200456 , version 1 (08-09-2023)

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F. Legendre, A. Heuze, K. Boukerrouche, S. Leclercq, K. Boumediene, et al.. Rhein, the metabolite of diacerhein, reduces the proliferation of osteoarthritic chondrocytes and synoviocytes without inducing apoptosis. Scandinavian Journal of Rheumatology, 2009, 38 (2), pp.104-111. ⟨10.1080/03009740802421996⟩. ⟨hal-04200456⟩
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