Matta Csaba, Zákány Róza, Mobasheri Ali
The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK,
Curr Rheumatol Rep. 2015 Jul;17(7):43. doi: 10.1007/s11926-015-0521-4.
Chondrocytes, the single cell type in adult articular cartilage, have conventionally been considered to be non-excitable cells. However, recent evidence suggests that their resting membrane potential (RMP) is less negative than that of excitable cells, and they are fully equipped with channels that control ion, water and osmolyte movement across the chondrocyte membrane. Amongst calcium-specific ion channels, members of the voltage-dependent calcium channel (VDCC) family are expressed in chondrocytes where they are functionally active. L-type VDCC inhibitors such as nifedipine and verapamil have contributed to our understanding of the roles of these ion channels in chondrogenesis, chondrocyte signalling and mechanotransduction. In this narrative review, we discuss published data indicating that VDCC function is vital for chondrocyte health, especially in regulating proliferation and maturation. We also highlight the fact that activation of VDCC function appears to accompany various inflammatory aspects of osteoarthritis (OA) and, based on in vitro data, the application of nifedipine and/or verapamil may be a promising approach for ameliorating OA severity. However, very few studies on clinical outcomes are available regarding the influence of calcium antagonists, which are used primarily for treating cardiovascular conditions in OA patients. This review is intended to stimulate further research on the chondrocyte 'channelome', contribute to the development of novel therapeutic strategies and facilitate the retargeting and repositioning of existing pharmacological agents currently used for other comorbidities for the treatment of OA.
软骨细胞是成年关节软骨中的唯一细胞类型，传统上被认为是不可兴奋细胞。然而，最近的证据表明，它们的静息膜电位（RMP）比可兴奋细胞的静息膜电位负性更小，并且它们完全具备控制离子、水和渗透溶质跨软骨细胞膜移动的通道。在钙特异性离子通道中，电压依赖性钙通道（VDCC）家族的成员在软骨细胞中表达，且在其中具有功能活性。硝苯地平和维拉帕米等L型VDCC抑制剂有助于我们了解这些离子通道在软骨形成、软骨细胞信号传导和机械转导中的作用。在这篇叙述性综述中，我们讨论已发表的数据，这些数据表明VDCC功能对软骨细胞健康至关重要，尤其是在调节增殖和成熟方面。我们还强调了这样一个事实，即VDCC功能的激活似乎伴随着骨关节炎（OA）的各种炎症方面，并且基于体外数据，应用硝苯地平和/或维拉帕米可能是改善OA严重程度的一种有前景的方法。然而，关于钙拮抗剂影响的临床结果研究非常少，钙拮抗剂主要用于治疗OA患者的心血管疾病。这篇综述旨在激发对软骨细胞“通道组”的进一步研究，促进新型治疗策略的开发，并促进目前用于其他合并症的现有药物重新靶向和重新定位以用于OA的治疗。
