Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides.
Mechanisms involved in enhancement of the expression and function of aggrecanases by hyaluronan oligosaccharides.
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DOI：
10.1002/art.33329
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发表时间：
2012-01
影响因子：
--
通讯作者：
Knudson, Warren
中科院分区：
文献类型：
--
作者：
Ariyoshi, Wataru;Takahashi, Nobunori;Hida, Daisuke;Knudson, Cheryl B.;Knudson, Warren
小透明质酸（HA）寡糖作为竞争性受体拮抗剂，从细胞表面取代HA并诱导细胞信号传导事件。在关节软骨细胞中，这种细胞信号传导由HA受体CD 44介导，并诱导刺激参与基质降解的基因，如基质金属蛋白酶以及基质修复基因，包括II型胶原蛋白、聚集蛋白聚糖和HA合酶-2。本研究的目的是确定软骨细胞CD 44-HA相互作用破坏后聚集蛋白聚糖酶的表达和功能的变化。牛关节软骨细胞或牛软骨组织在加入HA寡糖之前用多种主要信号传导途径的抑制剂预处理。通过真实的时间逆转录-聚合酶链反应和ADAMTS 4、ADAMTS 5和聚集蛋白聚糖蛋白水解片段的蛋白质印迹分析来监测聚集蛋白聚糖酶的变化。为了测试ADAMTS 4和MT4-MMP之间的相互作用，对从刺激的软骨细胞纯化的蛋白裂解物进行免疫共沉淀。破坏软骨细胞CD 44-HA与HA寡糖的相互作用以时间和剂量依赖性方式诱导ADAMTS 4和ADAMTS 5的转录。关节软骨细胞中HA寡糖也可诱导GPI锚定的MT4-MMP与ADAMTS 4的结合。抑制NF-κB通路阻断了HA寡糖介导的聚集蛋白聚糖酶刺激。HA寡糖对软骨细胞-基质相互作用的破坏性改变可诱导基质降解，并通过激活NF-κB信号通路提高聚集蛋白聚糖酶。
Small hyaluronan (HA) oligosaccharides serve as competitive receptor antagonists to displace HA from the cell surface and induce cell signaling events. In articular chondrocytes this cell signaling is mediated by the HA receptor CD44 and induces stimulation of genes involved in matrix degradation such as matrix metalloproteinases as well as matrix repair genes including collagen type II, aggrecan and HA synthase-2. The objective of this study was to determine changes in the expression and function of aggrecanases after disruption of chondrocyte CD44-HA interactions. Bovine articular chondrocytes or bovine cartilage tissue were pre-treated with a variety of inhibitors of major signaling pathways prior to the addition of HA oligosaccharides. Changes in aggrecanase were monitored by real time reverse transcriptase-polymerase chain reaction and western blot analysis of ADAMTS4, ADAMTS5 and aggrecan proteolytic fragments. To test the interactions between ADAMTS4 and MT4-MMP, protein lysates purified from stimulated chondrocytes were subjected to co-immunoprecipitation. Disruption of chondrocyte CD44-HA interactions with HA oligosaccharides induced the transcription of ADAMTS4 and ADAMTS5 in time- and dose-dependent manner. The association of GPI-anchored MT4-MMP with ADAMTS4 was also induced in articular chondrocytes by HA oligosaccharides. Inhibition of the NF-κB pathway blocked HA oligosaccharides-mediated stimulation of aggrecanases. Disruptive changes in chondrocyte-matrix interactions by HA oligosaccharides induce matrix degradation and elevate aggrecanases via the activation of the NF-κB signaling pathway.
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影响因子：
2.2
作者：
Naito, Satoko;Shiomi, Takayuki;Okada, Yasunori
通讯作者：
Okada, Yasunori
DOI：
10.1016/j.biocel.2005.08.011
发表时间：
2006-01-01
影响因子：
4
作者：
Iacob, S;Knudson, CB
通讯作者：
Knudson, CB
DOI：
10.1097/01.blo.0000143804.26638.82
发表时间：
2004-10-01
影响因子：
4.2
作者：
Knudson, CB;Knudson, W
通讯作者：
Knudson, W
影响因子：
4.8
作者：
Lyss, G;Knorre, A;Merfort, I
通讯作者：
Merfort, I
影响因子：
4.8
作者：
Itoh, Y;Kajita, M;Seiki, M
通讯作者：
Seiki, M