Emerging Multifunctional Roles of Claudin Tight Junction Proteins in Bone
Emerging Multifunctional Roles of Claudin Tight Junction Proteins in Bone
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DOI：
10.1210/en.2014-1173
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发表时间：
2014-07-01
期刊：
影响因子：
4.8
通讯作者：
Mohan, Subburaman
中科院分区：
文献类型：
--
作者：
Alshbool, Fatima Z.;Mohan, Subburaman
骨重塑过程中骨形成和吸收之间的不平衡已被证明是骨质疏松症发病机制的主要因素。最近的证据表明紧密连接蛋白 Claudins (Cldns) 在骨重塑过程的调节中发挥着重要作用。就功能而言，尽管 Cldns “规范地”充当细胞旁通透性的关键决定因素，但最近有大量证据表明 Cldns 也参与细胞信号传导，即“非规范功能”。为此，Cldns 已被证明可以调节多种细胞类型的细胞增殖、分化和基因表达。本综述将讨论 Cldns 的结构、表达谱、表达调节及其典型和非典型功能，特别强调骨细胞。为了阐明 Cldns 在骨中的非典型功能，我们将重点介绍 Cldn-18 在调节骨吸收和破骨细胞分化中的作用。总的来说，我们希望提供一个框架来指导未来的研究，了解 Cldns 如何调节成骨细胞和破骨细胞功能以及整体骨稳态。此类研究应该为骨质疏松症的发病机制提供有价值的见解，并可能强调 Cldns 作为骨质疏松症诊断和治疗管理的新靶点。
The imbalance between bone formation and resorption during bone remodeling has been documented to be a major factor in the pathogenesis of osteoporosis. Recent evidence suggests a significant role for the tight junction proteins, Claudins (Cldns), in the regulation of bone remodeling processes. In terms of function, whereas Cldns act "canonically" as key determinants of paracellular permeability, there is considerable recent evidence to suggest that Cldns also participate in cell signaling, ie, a "noncanonical function". To this end, Cldns have been shown to regulate cell proliferation, differentiation, and gene expression in a variety of cell types. The present review will discuss Cldns' structure, their expression profile, regulation of expression, and their canonical and non-canonical functions in general with special emphasis on bone cells. In order to shed light on the noncanonical functions of Cldns in bone, we will highlight the role of Cldn-18 in regulating bone resorption and osteoclast differentiation. Collectively, we hope to provide a framework for guiding future research on understanding how Cldns modulate osteoblast and osteoclast function and overall bone homeostasis. Such studies should provide valuable insights into the pathogenesis of osteoporosis, and may highlight Cldns as novel targets for the diagnosis and therapeutic management of osteoporosis.