Department of Anesthesiology, University Hospital Regensburg, 93042 Regensburg, Germany.
J Orthop Res. 2011 Jul;29(7):1114-20. doi: 10.1002/jor.21348. Epub 2011 Jan 31.
Cellular senescence is a program activated during diverse situations of cell stress. Chondrocytes differ from other somatic cells as articular cartilage is an avascular tissue. The effects of oxidative stress on chondrocytes are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of human osteoarthritic chondrocytes, subjected to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by RT-PCR. Sub-lethal doses of oxidative stress induced cell-cycle arrest, senescent-morphological features and senescence-associated β-galactosidase positivity. Prolonged oxidative treatment had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. The effects of sub-lethal oxidative stress regarding proliferation and telomere biology were more distinct in senescent cells. Acute oxidant insult caused up-regulation of p21 expression to levels comparable to senescent cells. TRF2 protects telomere ends and showed elevated expression levels. SIRT1 and XRCC5 enable cells to cope with unfavorable growing conditions. Both were up-regulated after oxidant insult, but expression levels decreased in aging cells. Taken together, oxidative stress considerably accelerated telomere shortening and cellular aging in chondrocytes. Senescent cells showed a reduced tolerance to oxidative stress.
细胞衰老（cellular senescence）是细胞在多种应激情况下激活的一种程序性细胞死亡。软骨细胞不同于其他体细胞，因为关节软骨是一种无血管组织。氧化应激对软骨细胞的影响尚不清楚。我们的研究旨在探讨人骨性关节炎软骨细胞在受到过氧化氢急性或长期氧化应激挑战时的增殖潜力、细胞学特征和端粒相关应激反应系统。端粒长度通过端粒限制片段分析进行测量，基因表达通过 RT-PCR 确定。亚致死剂量的氧化应激诱导细胞周期停滞、衰老形态特征和衰老相关的β-半乳糖苷酶阳性。延长氧化处理对细胞增殖或形态没有影响。亚致死和长期低剂量氧化应激会显著加速端粒磨损。亚致死氧化应激对增殖和端粒生物学的影响在衰老细胞中更为明显。急性氧化剂损伤导致 p21 表达上调至与衰老细胞相当的水平。TRF2 保护端粒末端，其表达水平升高。SIRT1 和 XRCC5 使细胞能够适应不利的生长条件。两者在氧化剂损伤后均上调，但在衰老细胞中表达水平下降。总之，氧化应激会显著加速软骨细胞中端粒缩短和细胞衰老。衰老细胞对氧化应激的耐受性降低。
