The role of integrin αvβ3 in osteocyte mechanotransduction
The role of integrin αvβ3 in osteocyte mechanotransduction
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DOI：
10.1016/j.jmbbm.2014.11.001
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发表时间：
2015-02-01
影响因子：
3.9
通讯作者：
McNamara, Laoise M.
中科院分区：
文献类型：
--
作者：
Haugh, Matthew G.;Vaughan, Ted J.;McNamara, Laoise M.
最近的体内研究提出，骨细胞细胞突起和细胞外基质之间的整合素α(v)β(3)附着可能促进骨中的机械感觉。然而，这些附着物在骨细胞对机械刺激的生化反应中的作用仍有待研究。考虑到这一点，本研究的目的是确定阻断整合素 α(v)β(3) 功能对骨细胞对机械刺激的生化反应的影响。使用整合素亚基β(3)特异性拮抗剂来阻断MLO-Y4小鼠骨细胞上的整合素α(v)β(3)。处理后，细胞受到层流振荡流体流刺激（1 Pa，1 Hz）一小时。进行荧光染色以观察细胞形态。使用酶免疫法测定前列腺素 E-2 (PGE(2)) 释放，并使用 qRT-PCR 分析环氧合酶-2 (COX-2)、NF-κ B 配体受体激活剂 (RANKL) 和骨保护素 (OPG) 的相对表达。我们的结果表明，阻断整合素 α(v)β(3) 会破坏骨细胞形态，导致扩散面积减少和过程回缩。整合素 α(v)β(3) 阻断还会破坏 COX-2 表达和响应流体剪切应力的 PGE(2) 释放。总而言之，这项研究的结果表明整合素α(v)β(3)对于骨细胞细胞过程的维持以及骨细胞的机械感觉和机械转导至关重要。更好地理解这一过程可能会导致机械敏感性被认为受到损害的骨病理学新疗法的开发。 (C) 2014 Elsevier Ltd. 保留所有权利。
Recent in vivo studies have proposed that integrin alpha(v)beta(3) attachments between osteocyte cell processes and the extracellular matrix may facilitate mechanosensation in bone. However the role of these attachments in osteocyte biochemical response to mechanical stimulus has yet to be investigated. With this in mind, the objective of this study was to determine the effect of blocking integrin alpha(v)beta(3) function on the biochemical response of osteocytes to mechanical stimulus. Antagonists specific to integrin subunit beta(3) were used to block integrin alpha(v)beta(3) on MLO-Y4 mouse osteocytes. After treatment, cells were subjected to laminar oscillatory fluid flow stimulus (1 Pa, 1 Hz) for one hour. Fluorescent staining was performed to visualise cell morphology. Prostaglandin E-2 (PGE(2)) release was assayed using an enzyme immunoassay and qRT-PCR was used to analyse the relative expression of cyclooxygenase-2 (COX-2), receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG). Our results show that blocking integrin alpha(v)beta(3) disrupts osteocyte morphology, causing a reduction in spread area and process retraction. Integrin alpha(v)beta(3) blocking also disrupted COX-2 expression and PGE(2) release in response to fluid shear stress. Taken together, the results of this study indicate that integrin alpha(v)beta(3) is essential for the maintenance of osteocyte cell processes and also for mechanosensation and mechanotransduction by osteocytes. A better understanding of this process may lead to the development of novel treatments for bone pathologies where mechanosensitivity is thought to be compromised. (C) 2014 Elsevier Ltd. All rights reserved.