Miao Yansong, Dong Yuefu, Huang Ping, Zhao Xiang, Huang Zhenyu, Yao Jufang, Li He, Xu Qingrong
Department of Orthopaedics, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Joint Surgery, The First People's Hospital of Lianyungang, Lianyungang, China.
Oncotarget. 2017 Jul 1;8(38):63750-63763. doi: 10.18632/oncotarget.18908. eCollection 2017 Sep 8.
The aim of this study is to demonstrate that improving the mitochondrial function can inhibite the loss of chondrocyte phenotype by regulating the expression of uncoupling protein 2(UCP2) and NADPH oxidase1/4(NOX1/4) to reduce the production of reactive oxygen species(ROS). The effects of mitochondrial biogenesis "master regular" peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcriptional factor A (TFAM), UCP2, and NOX1/4 on chondrocyte phenotype was examined. It was found that when the chondrocyte phenotype was lost, PGC-1α, UCP2, and TFAM expression decreased, while NOX1/4 expression increased. Inhibiting UCP2 expression promoted the loss of chondrocyte phenotype, and inhibiting NOX1/4 relieved the loss of the chondrocyte phenotype. After activating the PGC-1α-TFAM pathway, UCP2 increased and NOX1/4 decreased, which suppressed loss of the chondrocyte phenotype. After inhibiting NOX1/4, UCP2 expression increased. Increasing and decreasing UCP2 and NOX1/4 expression, respectively, helps maintain the chondrocyte phenotype and improve mitochondrial functioning by reducing reactive oxygen species production.
本研究的目的是证明改善线粒体功能可通过调节解偶联蛋白2（UCP2）和NADPH氧化酶1/4（NOX1/4）的表达来抑制软骨细胞表型的丧失，从而减少活性氧（ROS）的产生。研究了线粒体生物合成“主调节因子”过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、线粒体转录因子A（TFAM）、UCP2和NOX1/4对软骨细胞表型的影响。结果发现，当软骨细胞表型丧失时，PGC-1α、UCP2和TFAM的表达下降，而NOX1/4的表达增加。抑制UCP2表达促进软骨细胞表型丧失，抑制NOX1/4可缓解软骨细胞表型丧失。激活PGC-1α-TFAM途径后，UCP2增加而NOX1/4减少，从而抑制软骨细胞表型丧失。抑制NOX1/4后，UCP2表达增加。分别增加和减少UCP2和NOX1/4的表达，有助于维持软骨细胞表型并通过减少活性氧的产生来改善线粒体功能。
