Diacerein减少多余的骨重建的综合因素的人类成骨细胞细胞骨关节炎的软骨下骨。
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Pelletier JP,所说D, Reboul P, Mineau F,费尔南德斯JC, Sabouret P, Martel-Pelletier J
Diacerein减少多余的骨重建的综合因素的人类成骨细胞细胞骨关节炎的软骨下骨。
J Rheumatol。2001年4月,28 (4):814 - 24。
- PubMed ID
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11327257 (在PubMed]
- 文摘
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目的:尽管软骨退化特征骨关节炎(OA),有证据表明,软骨下骨的重塑这种疾病是一个因素。治疗策略修改软骨下骨成骨细胞的新陈代谢可能暗示治疗OA。我们研究的影响diacerein和大黄酸的代谢和炎症变量OA软骨下骨母细胞。方法:人类主要OA软骨下成骨细胞细胞。diacerein和大黄酸在治疗浓度的影响(5 - 20 microg /毫升)是由成骨细胞表型决定因素,碱性磷酸酶、骨钙素、和营;对代谢代理尿激酶纤溶酶原激活物(uPA)、纤溶酶原激活物inhibitor-1 (PAI-1)和胰岛素样生长因子- 1 (igf - 1);和炎症介质白介素6 (il - 6)、前列腺素E2 (PGE2)和cyclooxygenase-2 (cox - 2)。结果:Diacerein和大黄酸并不影响基底,25 (OH) 2 d3诱导碱性磷酸酶或甲状旁腺激素(素刺激阵营的形成。相反,他们剂量依赖性和统计抑制1,25 (OH) 2 d3诱导骨钙素的释放,一种情况解释为减少骨钙素mRNA水平。的代谢因素,抑制生产uPA、大黄酸显示稍微效力; inhibitions of 69% and 57% were reached at the highest concentration (20 microg/ml) of rhein and diacerein, respectively. Both drugs also inhibited the PAI-1 level, albeit at a much lower level than for uPA. Interestingly, determination of the uPA/PAI1 ratio revealed that both drugs inhibited it about 55%, suggesting a decrease in uPA activity. In contrast, IGF-1 levels only increased slightly when cells were treated with rhein but not with diacerein. A transient dose dependent effect was found on IL-6 production; an inhibition was noted at low drug concentrations, which returned to basal levels at the highest concentration tested. PGE2 levels increased exponentially and were related to a concomitant increase in COX-2 levels in response to both drugs. CONCLUSION: Our data indicate that diacerein and rhein do not appear to affect OA subchondral bone cells' basal cellular metabolism, yet both agents reveal a direct effect at reducing the synthetic activities of osteoblasts, which could be responsible for abnormal subchondral bone remodeling occurring during the course of OA.
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