CD95-induced osteoarthritic chondrocyte apoptosis and necrosis: dependency on p38 mitogen-activated protein kinase.
CD95-induced osteoarthritic chondrocyte apoptosis and necrosis: dependency on p38 mitogen-activated protein kinase.
复制标题
DOI：
10.1186/ar1891
复制
发表时间：
2006
影响因子：
4.9
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Wei L;Sun XJ;Wang Z;Chen Q
骨关节炎软骨的标志之一是由于细胞死亡而导致软骨细胞细胞结构的丧失。然而，最近围绕骨关节炎（OA）发展中涉及的细胞凋亡的程度引起了相当大的争议。为了阐明这个问题，我们表征了 CD95 (Fas) 通路介导的原代 OA 软骨细胞的细胞死亡。用抗CD95处理软骨细胞不仅增加了细胞死亡率，而且还增加了软骨细胞CD95配体的产生。这揭示了一种新的自分泌调节环路，活化的软骨细胞可以通过诱导 CD95 配体的合成来放大 CD95 信号。多种形态学检测分析表明，细胞凋亡仅导致软骨细胞死亡的一部分，而其他软骨细胞则因坏死而死亡。软骨细胞凋亡和坏死均取决于软骨细胞内 p38 丝裂原激活蛋白激酶 (MAPK) 的活性。用 p38 MAPK 抑制剂 SB203580 处理软骨细胞，通过抑制激活转录因子 2 和 caspase-3 的活性，消除了抗 CD95 诱导的细胞死亡。此外，5-溴-2-脱氧尿苷 (BrdU) 指数表明，抑制软骨细胞中的 p38 MAPK 活性会刺激软骨细胞增殖。因此，p38 MAPK 是一个潜在的治疗靶点，对其抑制可以通过抑制细胞死亡及其放大信号以及增加细胞增殖来维持关节软骨细胞的细胞结构。
One of the hallmarks of osteoarthritic cartilage is the loss of chondrocyte cellularity due to cell death. However, considerable controversy has recently arisen surrounding the extent of apoptotic cell death involved in development of osteoarthritis (OA). To shed light on this issue, we characterized cell death in primary OA chondrocytes mediated by the CD95 (Fas) pathway. Treatment of chondrocytes with anti-CD95 not only increased the rate of cell death but also increased the production of CD95 ligand by chondrocytes. This reveals a novel autocrine regulatory loop whereby activated chondrocytes may amplify CD95 signals by inducing synthesis of CD95 ligand. Multiple morphologic detection analyses indicated that apoptosis accounted for only a portion of chondrocyte death, whereas the other chondrocytes died by necrosis. Both chondrocyte apoptosis and necrosis depended on the activity of p38 mitogen-activated protein kinase (MAPK) within chondrocytes. Treatment of chondrocytes with the p38 MAPK inhibitor SB203580 abolished anti-CD95 induced cell death by inhibiting the activities of activating transcription factor-2 and caspase-3. In addition, inhibition of p38 MAPK activity in chondrocytes stimulated chondrocyte proliferation, as indicated by 5-bromo-2-deoxyuridine (BrdU) index. Thus, p38 MAPK is a potential therapeutic target, inhibition of which may maintain the cellularity of articular chondrocytes by inhibiting cell death and its amplification signal and by increasing cell proliferation.
登录
查看更多内容
影响因子：
2.7
作者：
CHEN, Q;JOHNSON, DM;GOETINCK, PF
通讯作者：
GOETINCK, PF
影响因子：
64.8
作者：
Reimold, AM;Grusby, MJ;Glimcher, LH
通讯作者：
Glimcher, LH
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M
影响因子：
27.4
作者：
Iannone, F;De Bari, C;Lapadula, G
通讯作者：
Lapadula, G
影响因子：
4.8
作者：
Sano, Y;Harada, J;Ishii, S
通讯作者：
Ishii, S