Inhibition of adenosine kinase attenuates interleukin-1-and lipopolysaccharide-induced alterations in articular cartilage metabolism
Inhibition of adenosine kinase attenuates interleukin-1-and lipopolysaccharide-induced alterations in articular cartilage metabolism
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DOI：
10.1016/j.joca.2004.12.004
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发表时间：
2005-03-01
影响因子：
7
通讯作者：
Benton, HP
中科院分区：
文献类型：
--
作者：
Petrov, R;MacDonald, MH;Benton, HP
目的：研究腺苷激酶抑制对白介素（IL）-1β-和脂多糖（LPS）诱导的软骨损伤的影响。稳定后，称重的软骨外植体暴露于IL-1β（10 ng/ml）或LPS（50 mu g/ml）中，以诱导软骨降解。为了测试腺苷的潜在保护作用，这些外植体同时暴露于腺苷（100 mU M），腺苷激酶抑制剂5'iodotubercidin（ITU，1 MU M）或腺苷和ITU。在培养物中72小时后，收集条件培养基以评估糖胺聚糖（GAG），一氧化氮（NO），前列腺素E-2（PGE（2））和基质金属蛋白酶（MMP）-3释放：IL-1 Beta。嘴唇刺激了堵嘴，NO，PGE（2）和MMP-3的显着释放。与ITU孵育可显着抑制IL-1β-和LPS诱导的GAG释放，但并未改变MMP-3产生。接触ITU还减少了IL-1β诱导的PGE2释放，而LPS诱导的无产生。直接补充腺苷的补充没有减弱IL-1β或LPS的影响，在没有IL-1β或LPS的情况下，添加腺苷或ITU在此模型中对软骨代谢没有任何可检测的作用。结论：腺苷激酶抑制剂ITU在体外软骨外植体模型中减弱了实验诱导的软骨损伤。从软骨细胞中释放腺苷可能在关节炎条件下对组织损伤的细胞反应中起作用，并且在关节中对这些途径的调节可能具有治疗关节炎的潜力。 （c）2005年国际骨关节炎研究协会。由Elsevier Ltd.出版。保留所有权利。
Objective: To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1 beta- and lipopolysaccharide (LPS)-induced cartilage damage.Design: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1 beta (10 ng/ml) or LPS (50 mu g/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 mu M), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 mu M) or to both adenosine and ITU. After 72 h in culture, conditioned medium was collected for evaluation of glycosaminoglycan (GAG), nitric oxide (NO), prostaglandin E-2 (PGE(2)) and matrix metalloproteinase (MMP)-3 release.Results: IL-1 beta and LIPS stimulated significant release of GAG, NO, PGE(2) and MMP-3. Incubation with ITU significantly inhibited both IL-1 beta- and LPS-induced GAG release, but did not alter MMP-3 production. Exposure to ITU also reduced IL-1 beta-induced PGE2 release and LPS-induced NO production. Direct adenosine supplementation did not attenuate the effects of IL-1 beta or LPS, and the addition of adenosine or ITU in the absence of IL-1 beta or LPS did not have any detectable effect on cartilage metabolism in this model.Conclusions: The adenosine kinase inhibitor ITU attenuated experimentally induced cartilage damage in an in vitro cartilage explant model. Release of adenosine from chondrocytes may play a role in the cellular response to tissue damage in arthritic conditions and modulation of these pathways in the joint may have potential for treatment of arthropathies. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.