Altered Integrin Mechanotransduction in Human Nucleus Pulposus Cells Derived From Degenerated Discs
Altered Integrin Mechanotransduction in Human Nucleus Pulposus Cells Derived From Degenerated Discs
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DOI：
10.1002/art.24248
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发表时间：
2009-02-01
影响因子：
--
通讯作者：
Hoyland, Judith Alison
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文献类型：
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作者：
Le Maitre, Christine Lyn;Frain, Jennie;Hoyland, Judith Alison
目标。一些研究已经证实了椎间盘(IVD)细胞对负荷的生物学反应，尽管机械转导途径尚未阐明。在表型类似于IVD细胞的关节软骨细胞中，已发现许多机械感受器，其中α5β1整合素是主要的机械感受器。本研究的目的是探讨整合素信号在机械刺激下IVD细胞中的作用，并确定是否与RGD整合素有关。人髓核(NP)细胞来源于非变性和退变的髓核细胞，在RGD抑制肽存在的情况下，承受动态压缩载荷。免疫组织化学方法检测IVD组织中α-5-β1异源二聚体的表达，实时定量聚合酶链式反应检测可能的机械受体。从非变性和退变的椎间盘中加载NP细胞后，Aggrecan基因的表达降低。在非退行性但不退化性静脉畸形的细胞中，用RGD多肽处理可抑制这种反应。免疫组织化学结果显示退行性IVD组织中α-5-β1异二聚体的表达与正常IVD组织相比无明显变化。我们的结果表明，退行性IVD细胞中的机械转导通路发生了改变。非变性椎间盘中的NP细胞通过RGD整合素进行机械传感，可能通过α5β1整合素，而变性椎间盘中的细胞表现出不同的信号通路，似乎不涉及RGD整合素。
Objective. Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with alpha 5 beta 1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.Methods. Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the alpha 5 beta 1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real-time quantitative polymerase chain reaction.Results. Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the alpha 5 beta 1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.Conclusion. Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the alpha 5 beta 1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.