ABSTRACT

Articular cartilage consists of an extracellular matrix including many proteins as well as embedded chondrocytes. Articular cartilage formation and function are influenced by mechanical forces. Hind limb unloading or simulated microgravity causes articular cartilage loss, suggesting the importance of the healthy mechanical environment in articular cartilage homeostasis and implying a significant role of appropriate mechanical stimulation in articular cartilage degeneration. Mechanosensitive ion channels participate in regulating the metabolism of articular chondrocytes, including matrix protein production and extracellular matrix synthesis. Mechanical stimuli, including fluid shear stress, stretch, compression and cell swelling and decreased mechanical conditions (such as simulated microgravity) can alter the membrane potential and regulate the metabolism of articular chondrocytes via transmembrane ion channel-induced ionic fluxes. This process includes Ca²⁺ influx and the resulting mobilization of Ca²⁺ that is due to massive released Ca²⁺ from stores, intracellular cation efflux and extracellular cation influx. This review brings together published information on mechanosensitive ion channels, such as stretch-activated channels (SACs), voltage-gated Ca²⁺ channels (VGCCs), large conductance Ca²⁺-activated K⁺ channels (BK_Ca channels), Ca²⁺-activated K⁺ channels (SK_Ca channels), voltage-activated H⁺ channels (VAHCs), acid sensing ion channels (ASICs), transient receptor potential (TRP) family channels, and piezo1/2 channels. Data based on epithelial sodium channels (ENaCs), purinergic receptors and N-methyl-d-aspartate (NMDA) receptors are also included. These channels mediate mechanoelectrical physiological processes essential for converting physical force signals into biological signals. The primary channel-mediated effects and signaling pathways regulated by these mechanosensitive ion channels can influence the progression of osteoarthritis during the mechanosensory and mechanoadaptive process of articular chondrocytes.

 抽象的

关节软骨由细胞外基质组成，其中包括许多蛋白质以及嵌入的软骨细胞。关节软骨的形成和功能受机械力的影响。后肢卸载或模拟微重力会导致关节软骨损失，这表明健康的机械环境在关节软骨稳态中的重要性，并意味着适当的机械刺激在关节软骨退化中具有重要作用。机械敏感离子通道参与调节关节软骨细胞的代谢，包括基质蛋白的产生和细胞外基质的合成。机械刺激，包括流体剪切应力、拉伸、压缩和细胞肿胀以及降低的机械条件（例如模拟微重力）可以改变膜电位并通过跨膜离子通道诱导的离子通量调节关节软骨细胞的代谢。该过程包括Ca ²⁺流入和由此产生的Ca ²⁺动员，这是由于从储存中大量释放Ca ²⁺ 、细胞内阳离子流出和细胞外阳离子流入。本综述汇集了有关机械敏感离子通道的已发表信息，例如拉伸激活通道 (SAC)、电压门控 Ca ²⁺通道 (VGCC)、大电导 Ca ²⁺激活 K ⁺通道（BK _Ca通道）、Ca ^{2 +} -激活的 K ⁺通道（SK _Ca通道）、电压激活的 H ⁺通道 (VAHC)、酸感应离子通道 (ASIC)、瞬时受体电位 (TRP) 家族通道和压电 1/2 通道。 还包括基于上皮钠通道 (ENaC)、嘌呤能受体和 N-甲基-d-天冬氨酸 (NMDA) 受体的数据。这些通道介导将物理力信号转化为生物信号所必需的机电生理过程。这些机械敏感离子通道调节的主要通道介导的效应和信号通路可以在关节软骨细胞的机械感觉和机械适应过程中影响骨关节炎的进展。