IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage

IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage
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DOI:
10.1016/s0945-053x(00)00111-6
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发表时间:
2000-11-01
期刊:
影响因子:
6.9
通讯作者:
Jones, SA
Jones, SA
中科院分区:
生物学1区
文献类型:
--
作者:
Flannery, CR;Little, CB;Jones, SA

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关节炎患者滑液和血清中白细胞介素 6 (IL-6) 和可溶性 IL-6 受体 (sIL-6R) 浓度升高与这些疾病相关的关节组织破坏有关,但迄今为止,关于 IL-6 在软骨蛋白聚糖 (聚集蛋白聚糖) 分解代谢过程中的作用和影响的研究是不同的。在本研究中,牛关节软骨外植体在存在或不存在IL-1α或TNF-α的情况下以及在有或没有IL-6和/或sIL-6R的共刺激下维持在模型器官培养系统中。测量外植体的蛋白聚糖损失后,评估每种培养条件的蛋白聚糖酶的蛋白水解活性和表达谱。用IL-6和/或sIL-6R刺激软骨外植体增强了聚集蛋白聚糖的分解代谢和释放,高于单独存在IL-1α或TNF-α时观察到的情况。这种分解代谢与聚集蛋白聚糖酶(但不是 MMP)活性相关,并与聚集蛋白聚糖酶 2 的 mRNA 表达相关。 (C) 2000 Elsevier Science B.V./国际基质生物学学会。版权所有。
Elevated concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) in the synovial fluids and serum of patients with arthritis have been implicated in the joint tissue destruction associated with these conditions, however studies conducted to date on the role and effects of IL-6 in the process of cartilage proteoglycan (aggrecan) catabolism are disparate. In the present study, bovine articular cartilage explants were maintained in a model organ culture system in the presence or absence of IL-1 alpha or TNF-alpha, and under co-stimulation with or without IL-6 and/or sIL-6R. After measuring proteoglycan loss from the explants, the proteolytic activity and expression profiles of aggrecanase(s) was assessed for each culture condition. Stimulation of cartilage explants with IL-6 and/or sIL-6R potentiated aggrecan catabolism and release above that seen in the presence of IL-1 alpha or TNF-alpha alone. This catabolism was associated with aggrecanase (but not MMP) activity, with correlative mRNA expression for aggrecanase-2. (C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.