Electrophysiological responses of human bone cells to mechanical stimulation: Evidence for specific integrin function in mechanotransduction
Electrophysiological responses of human bone cells to mechanical stimulation: Evidence for specific integrin function in mechanotransduction
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DOI：
10.1359/jbmr.1997.12.7.1133
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发表时间：
1997-07-01
影响因子：
6.2
通讯作者：
Wright, MO
中科院分区：
文献类型：
--
作者：
Salter, DM;Robb, JE;Wright, MO
骨细胞对机械刺激有反应，但其转导机制尚不完全清楚。整合素是一个异二聚体跨膜糖蛋白家族，它将细胞外基质的组分与肌动蛋白细胞骨架连接起来，被认为是机械感受器。我们评估了整合素在周期性机械刺激对人骨细胞（HBC）的转导中的作用，所述周期性机械刺激导致膜电位的变化，HBC在0.104 Hz机械刺激后显示膜去极化，在0.33 Hz刺激后显示膜超极化，膜去极化反应涉及河豚毒素敏感的钠通道，并且可以被抗α V的抗体抑制，β 1和β 5整合素。与此相反，超极化反应被钆和针对整合素相关蛋白（CD 47）、α 5和β 1整合素的抗体抑制。这两种反应都可以被含Arg-Gly-Asp（RGD）的肽、酪氨酸激酶活性的抑制和细胞骨架的破坏所消除。这些结果表明HBC对不同频率的机械应变的不同电生理反应。他们提出整联蛋白作为HBC机械感受器，具有不同的信号通路，被不同频率的机械刺激激活。
Bone cells respond to mechanical stimuli, but the transduction mechanisms responsible are not fully understood, Integrins, a family of heterodimeric transmembrane glycoproteins, which link components of the extracellular matrix with the actin cytoskeleton, have been implicated as mechanoreceptors. We have assessed the roles of integrins in the transduction of cyclical mechanical stimuli to human bone cells (HBCs), which results in changes in membrane potential, HBC showed membrane depolarization following 0.104 Hz mechanical stimulation and membrane hyperpolarization following stimulation at 0.33 Hz, The membrane depolarization response involved tetrodotoxin-sensitive sodium channels and could be inhibited by antibodies against alpha V, beta 1, and beta 5 integrins. In contrast, the hyperpolarization response was inhibited by gadolinium and antibodies to the integrin-associated protein (CD47), alpha 5 and beta 1 integrin, Both responses could be abrogated by Arg-Gly-Asp (RGD)-containing peptides, inhibition of tyrosine kinase activity, and disruption of the cytoskeleton, These results demonstrate differential electrophysiological responses of HBC to different frequencies of mechanical strain, Furthermore, they suggest that integrins act as HBC mechanoreceptors with distinct signaling pathways being activated by different frequencies of mechanical stimuli.