PDF(Pubmed)
Abstract：
Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1β (IL-1β) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1β-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.
摘要：
关节腔中持续的低渗和炎症状态可导致软骨基质丢失和细胞死亡，是骨关节炎(OA)发病的重要机制。先前的研究已经证实，低渗环境的存在是炎症的危险信号，由于低渗环境诱导细胞氯离子通道的开放并促进氯离子流出，这促使细胞体积增加。氯离子通道在矿化和软骨细胞死亡的调节中起着重要作用。这里,我们报道了OA软骨细胞的细胞死亡率和软骨基质分解代谢的失衡。我们发现骨架蛋白F-肌动蛋白的分布是无序的。此外,随着炎症相关蛋白caspase-1，caspase-3和NLRP3表达水平的增加，OA软骨细胞的体积敏感性氯离子电流显着降低。此外，白细胞介素-1β（IL-1β）显示出激活正常软骨细胞的氯离子电流的潜力。这些结果表明，IL-1β诱导的软骨细胞氯通道开放可能与OA的发生密切相关。因此,该氯化物通道打开过程可以是治疗OA的潜在目标。
