Growth-related oncogene α induction of apoptosis in osteoarthritis chondrocytes
Growth-related oncogene α induction of apoptosis in osteoarthritis chondrocytes
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DOI：
10.1002/art.10650
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发表时间：
2002-12-01
影响因子：
--
通讯作者：
Facchini, A
中科院分区：
文献类型：
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作者：
Borzi, RM;Mazzetti, I;Facchini, A
客观的。为了评估趋化因子生长相关癌基因 α (GROα) 的细胞凋亡作用，我们最近报道该基因在骨关节炎 (OA) 软骨细胞中表达上调。软骨细胞凋亡被认为是 OA 软骨损伤的主要决定因素，OA 是一种由软骨细胞异常产生炎症介质（细胞因子和趋化因子）和效应物（基质金属蛋白酶以及活性氧和氮物质）引起的疾病。我们通过常规方法（形态学、原位和溶液中 DNA 片段检测、磷脂酰丝氨酸暴露）和通过分析“早期”生化事件（质膜去极化、半胱天冬酶 3 激活和 c-Jun N 末端激酶/应激激活蛋白激酶磷酸化）研究了 GROalpha 对分离的人类细胞和体外培养的软骨外植体的凋亡作用。结果。我们清楚地证明了 GROalpha 能够引发一系列形态、生化和分子变化，导致软骨细胞凋亡。此外，我们发现从细胞外基质（ECM）传递的额外信号对于控制软骨细胞对 GROalpha 诱导的细胞凋亡的敏感性至关重要，因为只有在重新建立正确的相互作用 O 染色后刺激细胞时才能检测到细胞死亡。结论。 GROalpha 可以诱导关节软骨细胞凋亡，并且这种诱导依赖于来自 ECM 的额外信号。鉴于在这种风湿性疾病过程中关节间隙中存在 GROα 趋化因子，这些发现与了解 OA 的发病机制相关。
Objective. To evaluate the apoptotic effect of the chemokine growth-related oncogene alpha (GROalpha), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes.Methods. We investigated the apoptotic effect of GROalpha on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase).Results. We clearly demonstrated that GROalpha was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROalpha-induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interact O staining.Conclusion. GROalpha can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROalpha chemokine in the joint space in the course of this rheumatic disease.