Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M
Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M
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DOI：
10.1016/j.joca.2007.05.002
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发表时间：
2008-01-01
影响因子：
7
通讯作者：
Mort, J. S.
中科院分区：
文献类型：
--
作者：
Durigova, M.;Roughley, P. J.;Mort, J. S.
目的：探讨细胞因子组合对软骨蛋白多糖聚集分解代谢的协同和差异性作用。方法：在器官培养条件下，用细胞因子组合IL-1α(IL-1α)、IL-1β、IL-6、IL-17、肿瘤坏死因子α(TNFα)和抑瘤素M(OSM)刺激培养的牛关节软骨。分析了聚集素、连接蛋白和透明质酸(HA)的释放和降解，并考察了透明质酸酶抑制剂芹菜素的作用。结果：在所研究的所有细胞因子混合物中，聚集素仅通过聚集聚糖酶作用而发生明显的裂解。然而，OSM与IL-1或肿瘤坏死因子α协同作用时，由于聚集性和透明质酸的降解，可以迅速释放所有的蛋白多糖聚集成分。这一点被透明质酸酶抑制剂芹菜素所消除。此外，在OSM存在的情况下，还观察到一种低相对分子质量的聚集素G3产物，提示该细胞因子诱导聚集聚糖酶的裂解活性发生改变。结论：在细胞因子刺激下，聚集素从软骨中释放可能是通过聚集素核心蛋白的蛋白分解或通过透明质酸的解聚，后者的机制可能是由OSM诱导的。OSM与关节炎症有关，与骨性关节炎相比，OSM的参与可能是炎症性关节炎关节软骨中聚集素丢失更快的原因。(C)2007年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
objective: To investigate the potential synergistic and differential effects of cytokine combinations on proteoglycan aggregate catabolism in cartilage.Methods: Bovine articular cartilage explants were maintained in organ culture and subjected to stimulation with cytokine combinations including interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-17, tumor necrosis factor-alpha (TNF alpha) and oncostatin M (OSM). Aggrecan, link protein and hyaluronan (HA) release and degradation were analyzed, and the effect of the hyaluronidase inhibitor apigenin was investigated.Results: For all cytokine mixtures studied cleavage of aggrecan only by aggrecanase action was apparent. However, OSM acting synergistically with IL-1 or TNF alpha produced a rapid release of all proteoglycan aggregate components due to both aggrecan and HA degradation. This was abolished by the hyaluronidase inhibitor, apigenin. In addition, in the presence of OSM a low molecular weight aggrecan G3 product was observed, suggesting altered aggrecanase cleavage activity is induced by this cytokine.Conclusions: Under cytokine stimulation, aggrecan release from cartilage may take place via proteolysis of the aggrecan core protein or via depolymerization of HA, with the latter mechanism being induced by OSM. OSM is associated with joint inflammation and its participation may account for the more rapid loss of aggrecan from articular cartilage in the inflammatory arthritides, compared to osteoarthritis. (c) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.