Annexin A6 regulates catabolic events in articular chondrocytes via the modulation of NF-κB and Wnt/ß-catenin signaling.
Annexin A6 regulates catabolic events in articular chondrocytes via the modulation of NF-κB and Wnt/ß-catenin signaling.
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DOI：
10.1371/journal.pone.0197690
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kirsch T
中科院分区：
文献类型：
--
作者：
Minashima T;Kirsch T
膜联蛋白 A6 (AnxA6) 在关节软骨细胞中的表达水平高于其他间充质细胞类型。然而，AnxA6 在关节软骨细胞中的作用尚不清楚。在这里，我们表明，完全缺乏 AnxA6 功能导致 Wnt3a 处理的小鼠关节软骨细胞中 ß-catenin 活化增加，而表达 AnxA6 的关节软骨细胞则显示 ß-catenin 活化减少。 AnxA6 在人关节软骨细胞中的高表达显示出对 Wnt/ß-连环蛋白信号传导的最高抑制。 AnxA6 与胞质 Ca2+ 一起抑制 Wnt/β-catenin 信号活性是通过干扰 Wnt 信号复合物的质膜关联来实现的。 AnxA6 还通过降低 Wnt3a-、interleukin-1beta (IL-1ß)- 和组合 Wnt3a/IL-1ß 处理细胞中的 ß-catenin 活性并增加 NF-κB 活性，影响 Wnt/ß-catenin 信号传导和 NF-κB 信号传导之间的串扰。在人关节软骨细胞中，Wnt3a 治疗使分解代谢标志物（环氧合酶-2、白介素-6、诱导型一氧化氮合酶）的 mRNA 水平增加，其程度比 IL-1ß 治疗的程度要低得多，并且降低了基质金属蛋白酶-13 (MMP-13) 和关节软骨标志物（聚集蛋白聚糖、II 型胶原）的 mRNA 水平。此外，Wnt3a 降低了 IL-1ß 处理的人关节软骨细胞中分解代谢标记物和 MMP-13 的 mRNA 水平。 AnxA6的高表达导致Wnt3a处理的人关节软骨细胞中分解代谢标记物的mRNA水平降低，并且MMP-13和关节软骨标记物mRNA水平增加，而用IL-1ß或Wnt3a和IL-1ß组合处理的人关节软骨细胞中导致分解代谢标记物和MMP-13的mRNA水平增加。我们的研究结果通过调节 Wnt/ß-连环蛋白和 NF-κB 信号活动以及这两种信号通路之间的串扰，定义了 AnxA6 在关节软骨细胞中的新作用。
Annexin A6 (AnxA6) is expressed in articular chondrocytes at levels higher than in other mesenchymal cell types. However, the role of AnxA6 in articular chondrocytes is not known. Here we show that complete lack of AnxA6 functions resulted in increased ß-catenin activation in Wnt3a-treated murine articular chondrocytes, whereas AnxA6 expressing articular chondrocytes showed decreased ß-catenin activation. High expression of AnxA6 in human articular chondrocytes showed the highest inhibition of Wnt/ß-catenin signaling. Inhibition of Wnt/ß-catenin signaling activity by AnxA6 together with cytosolic Ca2+ was achieved by interfering with the plasma membrane association of the Wnt signaling complex. AnxA6 also affected the cross-talk between Wnt/ß-catenin signaling and NF-κB signaling by decreasing ß-catenin activity and increasing NF-κB activity in Wnt3a-, interleukin-1beta (IL-1ß)-, and combined Wnt3a/IL-1ß-treated cells. Wnt3a treatment increased the mRNA levels of catabolic markers (cyclooxygenase-2, interleukin-6, inducible nitric oxide synthase) to a much lesser degree than IL-1ß treatment in human articular chondrocytes, and decreased the mRNA levels of matrix metalloproteinase-13 (MMP-13) and articular cartilage markers (aggrecan, type II collagen). Furthermore, Wnt3a decreased the mRNA levels of catabolic markers and MMP-13 in IL-1ß-treated human articular chondrocytes. High expression of AnxA6 resulted in decreased mRNA levels of catabolic markers, and increased MMP-13 and articular cartilage marker mRNA levels in Wnt3a-treated human articular chondrocytes, whereas leading to increased mRNA levels of catabolic markers and MMP-13 in human articular chondrocytes treated with IL-1ß, or combined Wnt3a and IL-1ß. Our findings define a novel role for AnxA6 in articular chondrocytes via its modulation of Wnt/ß-catenin and NF-κB signaling activities and the cross-talk between these two signaling pathways.
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影响因子：
4
作者：
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通讯作者：
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影响因子：
6
作者：
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作者：
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DOI：
10.1016/j.bbrc.2004.07.124
发表时间：
2004-10-01
影响因子：
3.1
作者：
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通讯作者：
Moss, SE
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通讯作者：
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