Integrin α1β1 participates in chondrocyte transduction of osmotic stress.
Integrin α1β1 participates in chondrocyte transduction of osmotic stress.
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DOI：
10.1016/j.bbrc.2014.01.157
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发表时间：
2014-02-28
影响因子：
3.1
通讯作者：
Clark, Andrea L.
中科院分区：
文献类型：
--
作者：
Jablonski, Christina L.;Ferguson, Samuel;Pozzi, Ambra;Clark, Andrea L.
本研究的目的是确定胶原结合受体整合素α1β1在调节软骨细胞中炎症诱导的[Ca 2 +]i瞬变中的作用。采用实时共聚焦显微镜测量软骨细胞对渗透压的[Ca 2 +]i瞬时反应。对野生型和整联蛋白α1缺失小鼠的软骨细胞进行离体（在完整小鼠股骨的软骨中）和体外（从基质中分离，附着在盖玻片上）成像。进行免疫细胞化学以检测是否存在瞬时受体电位香草酸-4（TRPV 4），并使用激动剂GSK 1016790 A（GSK 101）检测其在野生型和整合素α1缺失小鼠软骨细胞上的功能。缺失整合素α1亚基可抑制软骨细胞对低渗应激的反应能力，[Ca 2 +]i瞬变离体和体外。软骨细胞的百分比响应离体小于在体外和响应的细胞，更多的单[Ca 2 +]i瞬变观察离体相比，在体外。免疫细胞化学证实了TRPV 4在野生型和整合素α1缺失的软骨细胞上的存在，然而，应用GSK 101揭示了TRPV 4可以在野生型而不是整合素α1缺失的软骨细胞上被激活。整合素α1β1是软骨细胞转导低渗应激的关键参与者。此外，整联蛋白α1β1影响β 1转导的机制不依赖于基质结合，但可能依赖于软骨细胞β 1受体TRPV 4。
The goal of this study was to determine the role of the collagen binding receptor integrin α1β1 in regulating osmotically induced [Ca2+]i transients in chondrocytes. The [Ca2+]i transient response of chondrocytes to osmotic stress was measured using real-time confocal microscopy. Chondrocytes from wildtype and integrin α1-null mice were imaged ex vivo (in the cartilage of intact murine femora) and in vitro (isolated from the matrix, attached to glass coverslips). Immunocytochemistry was performed to detect the presence of the osmosensor, transient receptor potential vanilloid-4 (TRPV4), and the agonist GSK1016790A (GSK101) was used to test for its functionality on chondrocytes from wildtype and integrin α1-null mice. Deletion of the integrin α1 subunit inhibited the ability of chondrocytes to respond to a hypo-osmotic stress with [Ca2+]i transients ex vivo and in vitro. The percentage of chondrocytes responding ex vivo was smaller than in vitro and of the cells that responded, more single [Ca2+]i transients were observed ex vivo compared to in vitro. Immunocytochemistry confirmed the presence of TRPV4 on wildtype and integrin α1-null chondrocytes, however application of GSK101 revealed that TRPV4 could be activated on wildtype but not integrin α1-null chondrocytes. Integrin α1β1 is a key participant in chondrocyte transduction of a hypo-osmotic stress. Furthermore, the mechanism by which integrin α1β1 influences osmotransduction is independent of matrix binding, but likely dependent on the chondrocyte osmosensor TRPV4.
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影响因子：
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通讯作者：
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