Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes
Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes
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DOI：
10.1016/j.biocel.2005.08.011
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Knudson, CB
中科院分区：
文献类型：
--
作者：
Iacob, S;Knudson, CB
软骨细胞CD44受体将透明质酸锚定在细胞表面，使蛋白聚糖聚集体能够在细胞周基质中组装和保留。透明质酸 - CD44相互作用也为维持软骨内稳态提供重要的信号传导。软骨细胞 - 透明质酸接触的中断会改变CD44的占位情况，引发其他信号级联反应。用透明质酸寡糖进行治疗是一种使CD44受体与其天然配体透明质酸解偶联的方法。在牛关节软骨细胞中，用透明质酸寡糖或纯化的透明质酸六糖处理可诱导产生一氧化氮，其情况与白细胞介素 - 1处理后一氧化氮的产生相似。相比之下，120和1260kDa的透明质酸不会诱导一氧化氮的产生。人类软骨细胞对透明质酸或透明质酸寡糖处理的反应类似。软骨细胞产生一氧化氮是由诱导型一氧化氮合酶的激活所介导的，这通过mRNA表达以及二亚苯基碘鎓对一氧化氮产生的抑制得以证实。用透明质酸寡糖和白细胞介素 - 1共同处理软骨细胞未显示出累加效应。用拮抗剂阻断白细胞介素 - 1受体并不能消除由透明质酸寡糖处理所诱导的一氧化氮的产生。此外，只有用pCD44转染后的COS - 7细胞，而非CD44缺失的亲本细胞，会因透明质酸寡糖处理而释放一氧化氮。这项研究表明，透明质酸片段具有一种新的信号传导潜能，它取代了内源性透明质酸 - 软骨细胞相互作用，导致诱导型一氧化氮合酶的激活。（c）2005爱思唯尔有限公司。保留所有权利。
Chondrocyte CD44 receptors anchor hyaluronan to the cell surface, enabling the assembly and retention of proteoglycan aggregates in the pericellular matrix. Hyaluronan-CD44 interactions also provide signaling important for maintaining cartilage homeostasis. Disruption of chondrocyte-hyaluronan contact alters CD44 occupancy, initiating alternative signaling cascades. Treatment with hyaluronan oligosaccharides is one approach to uncouple CD44 receptors from its native ligand, hyaluronan. In bovine articular chondrocytes, treatment with hyaluronan oligosaccharides or purified hyaluronan hexasaccharides induced the production of nitric oxide that mirrored nitric oxide production following interleukin-1 treatment. In contrast, 120 and 1260kDa hyaluronan did not induce production of nitric oxide. Human chondrocytes responded similarly to treatment with hyaluronan or hyaluronan oligosaccharides. Nitric oxide production from chondrocytes was mediated by activation of the inducible nitric oxide synthase, as confirmed by mRNA expression and inhibition of nitric oxide production by diphenyleneiodonium. Co-treatment of chondrocytes with hyaluronan oligosaccharides and interleukin-1 did not demonstrate additive effects. Blocking interleukin-1 receptors with an antagonist did not abolish the production of nitric oxide induced by treatment with hyaluronan oligosaccharides. Moreover, only COS-7 following transfection with a pCD44, not the CD44-null parental cells, responded to treatment with hyaluronan oligosaccharides by releasing nitric oxide. This study demonstrates a novel signaling potential by hyaluronan fragments, in lieu of endogenous hyaluronan-chondrocyte interactions, resulting in the activation of inducible nitric oxide synthase. (c) 2005 Elsevier Ltd. All rights reserved.