Synthesis and release of human cartilage matrix proteoglycans are differently regulated by nitric oxide and prostaglandin-E2
Synthesis and release of human cartilage matrix proteoglycans are differently regulated by nitric oxide and prostaglandin-E2
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DOI：
10.1136/ard.2006.065946
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发表时间：
2008-01-01
影响因子：
27.4
通讯作者：
Lafeber, F. P. J. G.
中科院分区：
文献类型：
--
作者：
Mastbergen, S. C.;Bijlsma, J. W. J.;Lafeber, F. P. J. G.
目的：最近的研究表明，考克斯-2抑制对IL-1 β/肿瘤坏死因子α（TNF α）损伤的软骨和骨关节炎软骨的蛋白聚糖周转具有有益作用。虽然蛋白多糖释放和含量正常化，蛋白多糖合成只有部分影响。前列腺素E-2是考克斯-2形成的主要产物。因此，我们评估的作用，在干扰软骨蛋白多糖turning.Methods：人健康的软骨，单独或在IL-1 β +TNF α的存在下，与或不与Eglandin-E-2或选择性考克斯-2抑制剂（塞来昔布10 μ M）培养7天。结果：软骨基质蛋白多糖的合成和释放均不受单独使用野牡丹素-E-2的影响。向健康软骨中加入IL-1 β +TNF α可抑制蛋白聚糖合成并增加蛋白聚糖释放。当除了IL-1 β +TNF α外，还加入了野牡丹素-E-2时，蛋白聚糖的释放进一步增加，但蛋白聚糖的合成没有受到进一步的影响。在IL-1 β +TNF α处理的软骨中加入选择性考克斯-2抑制剂，抑制了增强的胰高血糖素-E-2的产生，几乎完全使蛋白多糖的释放正常化，而合成不受影响。此外，增强的NO水平仍然升高。前列腺素-E-2水平与蛋白多糖释放显着相关，而NO水平与蛋白多糖synthesization.Conclusion：目前的结果表明，参与增强软骨蛋白多糖释放，但不合成，虽然健康的软骨已被致敏IL-1 β +肿瘤坏死因子α（TNF α）的前列腺素-E-2。IL-1 β +TNF α诱导的NO似乎参与抑制蛋白多糖合成，不依赖于胰高血糖素-E-2，因此似乎对（选择性）考克斯-2抑制剂的调节不敏感。
Objectives: Recent studies showed beneficial effects of COX-2 inhibition on proteoglycan turnover of both IL-1 beta/tumour necrosis factor a (TNF alpha) damaged cartilage and of osteoarthritic cartilage. Although proteoglycan release and content were normalised, proteoglycan synthesis was only partially influenced. Prostaglandin-E-2 is the main product formed by COX-2. We therefore evaluate the role of prostaglandin-E-2 in relation to nitric oxide in disturbing cartilage proteoglycan turnover.Methods: Human healthy cartilage, alone or in the presence of IL-1 beta+TNF alpha, was cultured for 7 days with or without prostaglandin-E-2 or the selective COX-2 inhibitor (celecoxib 10 mu M). Changes in cartilage matrix proteoglycan turnover, levels of prostaglandin-E-2 and nitric oxide were determined.Results: Proteoglycan synthesis and release of the cartilage were not affected by prostaglandin-E-2 alone. Addition of IL-1 beta+TNF alpha to healthy cartilage resulted in inhibition of proteoglycan synthesis and increase in proteoglycan release. When prostaglandin-E-2 was added, in addition to IL-1 beta+TNF alpha, proteoglycan release increased further, but proteoglycan synthesis was not influenced further. Addition of a selective COX-2 inhibitor to the IL-1 beta+TNF alpha treated cartilage inhibited the enhanced prostaglandin-E-2 production and almost completely normalised proteoglycan release, whereas synthesis remained unaffected. Also, the enhanced NO-levels remained elevated. Prostaglandin-E-2 levels correlated significantly with proteoglycan release, whereas NO levels correlated significantly with proteoglycan synthesis.Conclusion: The present results suggest involvement of prostaglandin-E-2 in enhanced cartilage proteoglycan release but not synthesis, although healthy cartilage has to be sensitised by IL-1 beta+tumour necrosis factor alpha (TNF alpha). IL-1 beta+TNF alpha induced NO seems to be involved in inhibition of proteoglycan synthesis, independent of prostaglandin-E-2, and thus seems insensitive to regulation by (selective) COX-2 inhibitors.