Lee Mel S, Trindade Michael C D, Ikenoue Takashi, Goodman Stuart B, Schurman David J, Smith Robert Lane
Stanford University School of Medicine, Stanford, California 94305, USA.
J Cell Biochem. 2003 Sep 1;90(1):80-6. doi: 10.1002/jcb.10611.
Onset and progression of cartilage degeneration is associated with shear stress occurring in diarthrodial joints subjected to inappropriate loading. This study tested the hypothesis that shear stress induced nitric oxide is associated with altered expression of regulatory onco-proteins, bcl-2, and Fas (APO-1/CD95) and apoptosis in primary human osteoarthritic chondrocyte cultures. Shear stress induced membrane phosphatidylserine and nucleosomal degradation were taken as evidence of chondrocyte apoptosis. Application of shear stress upregulated nitric oxide in a dose-dependent manner and was associated with increases in membrane phosphatidylserine and nucleosomal degradation. Increasing levels of shear stress decreased expression of the anti-apoptotic factor, bcl-2, from 44 to 10 U/ml. Addition of the nitric oxide antagonists, L-N(5)-(1-iminoethyl) ornithine and Nomega-nitro-L-arginine methyl ester (L-NAME), reduced shear stress induced nucleosomal degradation by 62% and 74%, respectively. Inhibition of shear stress induced nitric oxide release by L-NAME coincided with a 2.7-fold increase of bcl-2, when compared to chondrocytes exposed to shear stress in the absence of L-NAME. These data suggest that shear stress induced nitric oxide is associated with changes in apoptotic regulatory factors that alter chondrocyte metabolism and may contribute to joint degeneration.
软骨退变的发生和进展与承受不当负荷的滑膜关节中出现的剪切应力有关。本研究检验了以下假设：剪切应力诱导的一氧化氮与原代人骨关节炎软骨细胞培养物中调节癌蛋白、bcl-2和Fas（APO-1/CD95）表达的改变以及细胞凋亡有关。剪切应力诱导的膜磷脂酰丝氨酸和核小体降解被视为软骨细胞凋亡的证据。施加剪切应力以剂量依赖方式上调一氧化氮，并与膜磷脂酰丝氨酸和核小体降解增加有关。剪切应力水平增加使抗凋亡因子bcl-2的表达从44 U/ml降至10 U/ml。添加一氧化氮拮抗剂L-N(5)-(1-亚氨基乙基)鸟氨酸和Nω-硝基-L-精氨酸甲酯（L-NAME）分别使剪切应力诱导的核小体降解减少62%和74%。与在无L-NAME情况下暴露于剪切应力的软骨细胞相比，L-NAME抑制剪切应力诱导的一氧化氮释放与bcl-2增加2.7倍同时发生。这些数据表明，剪切应力诱导的一氧化氮与凋亡调节因子的变化有关，这些变化改变软骨细胞代谢并可能导致关节退变。
