Association of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments
Association of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments
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DOI：
10.1006/abbi.1996.0461
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发表时间：
1996-10-15
影响因子：
3.9
通讯作者：
Hui, F
中科院分区：
文献类型：
--
作者：
Homandberg, GA;Hui, F
将纤连蛋白片段添加到牛关节软骨外植体培养物中导致金属蛋白酶的释放增强和软骨蛋白聚糖（PG）的快速降解和损失。软骨溶解开始于PG的快速降解，1周后明显减慢。初步观察表明，分解代谢细胞因子介导的纤维连接蛋白片段的软骨溶解活性。本研究的目的是研究以下因素之间的相关性：（a）特定细胞因子的释放;（B）金属蛋白酶（MMP），基质溶解素-1（MMP-3）的释放;（c）MMP的组织抑制剂TIMP-1的释放;（d）培养软骨中PG的降解和释放。我们报告说，人关节软骨培养的氨基末端29 kDa片段（Fn-f），在0.1 μ M，释放增强水平的TNF-α，IL-1 β，IL-1 α的峰值分别在第2，3和9天。MMP-3释放升高，在第6天达到峰值，并且曲线与Fn-f诱导的软骨PG消耗相似。IL-6的释放在2天内增强，并在整个培养期间持续相同的水平，但这并不导致TIMP-1的释放增强，TIMP-1是IL-6的一种已知活性。这些数据表明，在Fn-f在培养软骨中诱导的早期软骨溶解事件中，培养软骨中MMP-3释放的增强和PG的最大降解和释放与分解代谢细胞因子TNF-α、IL-1 β和IL-1 α的释放升高在动力学上相关。此外，PG损失减缓和MMP-3释放减缓的后期与这些细胞因子的释放大大减缓有关，但IL-6的释放延长。这种软骨损伤模型可能有助于研究细胞因子之间的相互作用以及细胞因子组合对软骨稳态的影响。(C)出版社：Academic Press，Inc.
Addition of fibronectin fragments to bovine articular cartilage explant cultures results in enhanced release of metalloproteinases and rapid cartilage proteoglycan (PG;) degradation and loss. The chondrolysis begins with rapid PG degradation which markedly slows after 1 week. Preliminary observations suggest that catabolic cytokines mediate chondrolytic activities of the fibronectin fragments. The objectives of this work were to investigate the correlations between: (a) release of specific cytokines; (b) release of the metalloproteinase (MMP), stromelysin-1 (MMP-3); (c) release of the tissue inhibitor of MMPs, TIMP-1, and; (d) degradation and release of PG from cultured cartilage. We report that human articular cartilage cultured with an amino-terminal 29-kDa fragment (Fn-f), at 0.1 mu M, released enhanced levels of TNF-alpha, IL-1 beta, and IL-1 alpha with peaks at Days 2, 3, and 9, respectively. MMP-3 release was elevated with a peak at Day 6 and a profile similar to that for the Fn-f-induced cartilage PG depletion. IL-6 release was enhanced within 2 days and continued at the same level throughout the culture period but this did not lead to enhanced release of TIMP-1, a known activity of IL-6. These data suggest that in the early chondrolytic events induced in cultured cartilage by Fn-f, enhanced MMP-3 release and maximal degradation and release of PG from cultured cartilage are kinetically associated with elevated release of the catabolic cytokines, TNF-alpha, IL-1 beta, and IL-1 alpha. Further, a later period of slowing PG loss and slowing MMP-3 release is associated with greatly slowed release of these cytokines, but prolonged release of IL-6. This model of cartilage damage may be useful for studies of the interplay between cytokines and the effects of combinations of cytokines on cartilage homeostasis. (C) 1996 Academic Press, Inc.