Endoplasmic reticulum stress inhibits collagen synthesis independent of collagen-modifying enzymes in different chondrocyte populations and dermal fibroblasts.
Endoplasmic reticulum stress inhibits collagen synthesis independent of collagen-modifying enzymes in different chondrocyte populations and dermal fibroblasts.
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DOI：
10.1139/o09-174
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发表时间：
2010-05
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影响因子：
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通讯作者：
L. Vonk;B. Doulabi;Chunling Huang;M. Helder;V. Everts;R. Bank
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作者：
L. Vonk;B. Doulabi;Chunling Huang;M. Helder;V. Everts;R. Bank
软骨细胞对葡萄糖剥夺的反应是由于内质网（ER）的正常功能被破坏而导致胶原蛋白合成减少：ER应激。由于参与合成减少的机制是未知的，我们已经调查了是否伴侣和胶原修饰酶的葡萄糖剥夺的影响。从髓核、纤维环、关节软骨和半月板获得的软骨细胞和真皮成纤维细胞在对照条件下培养或暴露于衣霉素添加或葡萄糖撤回的ER应激诱导处理。这两种治疗方法导致所有细胞类型中ER应激标志物的基因表达上调，但真皮成纤维细胞对葡萄糖剥夺的反应延迟。胶原基因表达下调，和较少的胶原蛋白存在于两个ER应激诱导条件下的细胞。脯氨酰4-羟化酶的表达水平不受影响（P4 ha 3）或增加（P4 ha 1和P4 ha 2），赖氨酰羟化酶的水平降低，N-前肽酶Adamts 2降低。两种处理均诱导细胞凋亡。软骨细胞对葡萄糖剥夺的反应更快，但似乎软骨细胞比成纤维细胞更能科普衣霉素诱导的ER应激。虽然胶原蛋白的合成受到抑制的治疗，一些胶原蛋白修饰酶和分子伴侣上调，这表明它们之间没有因果关系。
Chondrocytes respond to glucose deprivation with a decreased collagen synthesis due to disruption of a proper functioning of the endoplasmic reticulum (ER): ER stress. Since the mechanisms involved in the decreased synthesis are unknown, we have investigated whether chaperones and collagen-modifying enzymes are affected by glucose deprivation. Chondrocytes obtained from nucleus pulposus, annulus fibrosus, articular cartilage, and meniscus and dermal fibroblasts were cultured under control conditions or exposed to the ER stress-inducing treatments of tunicamycin addition or glucose withdrawal. Both treatments resulted in an up-regulation of the gene expression of the ER stress markers in all cell types, but dermal fibroblasts showed a delayed response to glucose deprivation. Collagen gene expression was down-regulated, and less collagen protein was present in the cells under both ER stress-inducing conditions. The expression levels of the prolyl 4-hydroxylases were either not affected (P4ha3) or increased (P4ha1 and P4ha2), the levels of the lysyl hydroxylases decreased, and the N-propeptidase Adamts2 decreased. Both treatments induced apoptosis. Chondrocytes respond more quickly to glucose deprivation, but it appears that chondrocytes can cope better with tunicamycin-induced ER stress than fibroblasts. Although collagen synthesis was inhibited by the treatments, some collagen-modifying enzymes and chaperones were up-regulated, suggesting that there is no causal relation between them.