Department of Veterinary Pre-Clinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Queen's Medical Centre, Nottingham, United Kingdom; Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Joint Bone Spine. 2019 Jan;86(1):29-35. doi: 10.1016/j.jbspin.2018.01.012. Epub 2018 Feb 13.
Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with "moonlighting" roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.
软骨细胞是关节软骨细胞外基质 (ECM) 的主要细胞，具有高度分化的表型，这是这种特殊的承重结缔组织独特生理功能的标志。关节软骨细胞的质膜含有丰富多样的膜蛋白，称为膜蛋白质组，它定义了细胞的表面表型。膜蛋白质组是药物的主要靶点，对软骨细胞的功能很重要。它包括通道、转运蛋白、酶、受体以及细胞内、细胞骨架和 ECM 蛋白和其他大分子复合物的锚定蛋白。软骨细胞通道组是膜蛋白质组的一个亚组，其中包括在这些细胞中表达的一整套离子通道和孔蛋白。其中许多是多功能蛋白，具有“兼职”作用，充当通道、受体和更大分子组装的信号成分。这篇综述的目的是总结我们目前对软骨细胞通道组的基本方面的认识，讨论其与软骨生物学的相关性，并强调其在骨关节炎 (OA) 发病机制中的可能作用。过度和不适当的机械负荷、炎症微环境、通道成分的选择性剪接或基础磷酸钙晶体的积累会导致软骨细胞通道组发生改变，从而损害其功能。Ca 信号的改变可能导致 ECM 大分子的合成缺陷和软骨细胞中分解代谢反应的加剧，这是 OA 发展的复杂且了解甚少的机制的一个重要且相对未被探索的方面。
