Abstract:
OBJECTIVE:The primary objective of this study was to evaluate the ex vivo therapeutic efficacy of diacerein and its active metabolite, rhein, on osteoarthritic (OA) cartilage chondrocyte DNA fragmentation and death in the experimental canine model of OA. The study also aimed to explore the effect of the drug on the level of important factors involved in this phenomenon, i.e., caspase-3 and inducible nitric oxide synthase (iNOS). METHODS:OA knee cartilage was obtained from dogs that had received surgical sectioning of the anterior cruciate ligament (ACL) and were sacrificed 12 weeks after surgery. Cartilage explants were cultured in the presence or absence of therapeutic concentrations of diacerein (20 micrograms/ml) or rhein (20 micrograms/ml). Cartilage specimens were stained for TUNEL reaction and immunostained using specific antibodies for active caspase-3 and iNOS. Morphometric analyses were also performed. RESULTS:In OA cartilage specimens, a large number of chondrocytes in the superficial layers stained positive for TUNEL reaction. Treatment with therapeutic concentrations of diacerein (20 micrograms/ml) or rhein (20 micrograms/ml) significantly reduced the level of chondrocyte DNA fragmentation to about the same extent in both treatment groups (P < 0.006, P < 0.002, respectively). The levels of caspase-3 and iNOS in cartilage explants were also significantly decreased (caspase-3, diacerein P < 0.04; caspase-3, rhein P < 0.0003; and iNOS, rhein P < 0.009, respectively) when compared to the control group. CONCLUSIONS:This study shows that diacerein/rhein can effectively reduce the level of OA chondrocyte DNA fragmentation and death under the present experimental conditions. This effect is mediated by a decrease in the level of caspase-3 expression, which could possibly be related in part to the reduced level of iNOS and secondarily to NO production. These findings provide additional new information about the mechanisms of action of diacerein on the progression of OA.
journal_name
Clin Exp Rheumatoljournal_title
Clinical and experimental rheumatologyauthors
Pelletier JP,Mineau F,Boileau C,Martel-Pelletier Jkeywords:
subject
Has Abstractpub_date
2003-03-01 00:00:00pages
171-7issue
2eissn
0392-856Xissn
1593-098Xjournal_volume
21pub_type
杂志文章abstract::Early arthritis is challenging because the clinical picture often does not allow a distinction between rheumatoid arthritis (RA), self-limiting disease, and other forms of inflammatory arthritis. In Germany the first early synovitis clinic and several inception cohorts of patients with early RA were initiated and eval...
journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,评审
doi:
更新日期:2003-09-01 00:00:00
abstract::This review contrasts the difficulty of differentiating early rheumatoid arthritis (RA) from the many other causes of inflammatory polyarthritis and emphasizes the need for early treatment of RA with drugs that are present considered inappropriate for a mild, self-limiting disease. Pointers to help establish a definit...
journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,评审
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journal_title:Clinical and experimental rheumatology
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journal_title:Clinical and experimental rheumatology
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journal_title:Clinical and experimental rheumatology
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journal_title:Clinical and experimental rheumatology
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,meta分析,评审
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更新日期:2017-07-01 00:00:00
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journal_title:Clinical and experimental rheumatology
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更新日期:1996-05-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,评审
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更新日期:2019-09-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,多中心研究
doi:
更新日期:2015-05-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
更新日期:2014-01-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2013-07-01 00:00:00
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journal_title:Clinical and experimental rheumatology
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doi:
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章,评审
doi:
更新日期:2013-03-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
更新日期:2015-01-01 00:00:00
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journal_title:Clinical and experimental rheumatology
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doi:
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doi:
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journal_title:Clinical and experimental rheumatology
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doi:
更新日期:2013-05-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
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更新日期:1990-07-01 00:00:00
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journal_title:Clinical and experimental rheumatology
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doi:
更新日期:2013-03-01 00:00:00
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journal_title:Clinical and experimental rheumatology
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
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journal_title:Clinical and experimental rheumatology
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doi:
更新日期:1997-11-01 00:00:00
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