软骨机械转导中的整合素、钙粘蛋白和通道:对未来再生策略的展望。

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Reviews in Molecular Medicine Pub Date : 2021-10-27 DOI:10.1017/erm.2021.16
Martin Philipp Dieterle, Ayman Husari, Bernd Rolauffs, Thorsten Steinberg, Pascal Tomakidi
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引用次数: 18

摘要

关节软骨由透明软骨组成,是人类肌肉骨骼系统的主要组成部分,在无摩擦关节运动和关节稳态中具有关键功能。骨关节炎(OA)是一种关节软骨炎症性疾病,可促进关节退化。尽管它影响着数百万人,但没有令人满意的疗法可以在分子水平上解决这种疾病。因此,组织再生方法旨在改变软骨细胞生物学,以减轻OA的后果。这需要对细胞进行适当的生物化学和生物物理刺激。关于后者,软骨细胞及其前体细胞的机械转导在过去几十年中变得越来越重要。机械转导是将外部生物物理刺激转化为细胞内生物化学信号,涉及细胞表面的传感器分子和细胞内信号分子,即所谓的机械传感器和换能器。这些信号事件决定了细胞的行为。机制转化离子通道和间隙连接另外控制软骨细胞的生理学。通过控制这些机械转导途径来诱导特定的细胞行为,并将这些知识转化为再生临床疗法,具有重大的科学和医学意义。因此,本文综述了软骨组织中整合素、钙粘蛋白和离子通道的机械转导特性,为软骨再生提供了前景。
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Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies.

Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level. Therefore, tissue regeneration approaches aim at modifying chondrocyte biology to mitigate the consequences of OA. This requires appropriate biochemical and biophysical stimulation of cells. Regarding the latter, mechanotransduction of chondrocytes and their precursor cells has become increasingly important over the last few decades. Mechanotransduction is the transformation of external biophysical stimuli into intracellular biochemical signals, involving sensor molecules at the cell surface and intracellular signalling molecules, so-called mechano-sensors and -transducers. These signalling events determine cell behaviour. Mechanotransducing ion channels and gap junctions additionally govern chondrocyte physiology. It is of great scientific and medical interest to induce a specific cell behaviour by controlling these mechanotransduction pathways and to translate this knowledge into regenerative clinical therapies. This review therefore focuses on the mechanotransduction properties of integrins, cadherins and ion channels in cartilaginous tissues to provide perspectives for cartilage regeneration.

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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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