Seo Yo-Seob, Cho In-A, Kim Tae-Hyeon, You Jae-Seek, Oh Ji-Su, Lee Gyeong-Je, Kim Do Kyung, Kim Jae-Sung
Department of Oral and Maxillofacial Radiology, Chosun University, Gwangju 61452, Korea.
Institute of Dental Science, Chosun University, Gwangju 61452, Korea.
Korean J Physiol Pharmacol. 2020 May 1;24(3):249-257. doi: 10.4196/kjpp.2020.24.3.249.
The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25-HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspase-dependent apoptosis, but also induced proteoglycan loss in articular cartilage cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.
本研究的目的是探讨骨关节炎的病理生理病因，其由暴露于25-羟基胆固醇（25-HC）的软骨细胞凋亡介导，25-HC是一种在炎症条件下由胆固醇-25-羟化酶（CH25H）表达合成的氧化甾醇。白细胞介素-1β以剂量依赖性方式诱导软骨细胞凋亡。此外，通过CH25H的表达，在白细胞介素-1β处理的软骨细胞中25-HC的产生增加。25-HC降低了软骨细胞的活力。25-HC使细胞核浓缩的软骨细胞和凋亡细胞群体增加。此外，在用25-HC处理的软骨细胞中，死亡配体介导的外源性和线粒体依赖性内源性凋亡途径增加了caspase-3的活性和表达。最后，25-HC不仅诱导了caspase依赖性凋亡，还诱导了培养的大鼠膝关节软骨中蛋白聚糖的丢失。这些数据表明，25-HC可能作为骨关节炎中的一种代谢病理生理因素，其由炎症条件下关节软骨中软骨细胞的渐进性死亡介导。
