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学科主题: 临床医学
题名:
Proinflammatory Cytokines Stimulate Mitochondrial Superoxide Flashes in Articular Chondrocytes In Vitro and In Situ
作者: Cao, Yongxing1; Zhang, Xin1; Shang, Wei2; Xu, Jiejia2; Wang, Xianhua2; Hu, Xiaoqing1; Ao, Yingfang1; Cheng, Heping2
刊名: PLOS ONE
发表日期: 2013-06-19
DOI: 10.1371/journal.pone.0066444
卷: 8, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: OXIDATIVE-STRESS ; CARTILAGE ; OSTEOARTHRITIS ; METABOLISM ; APOPTOSIS ; DISEASE ; SURFACE
英文摘要:

Objective: Mitochondria play important roles in many types of cells. However, little is known about mitochondrial function in chondrocytes. This study was undertaken to explore possible role of mitochondrial oxidative stress in inflammatory response in articular chondrocytes.

Methods: Chondrocytes and cartilage explants were isolated from wild type or transgenic mice expressing the mitochondrial superoxide biosensor - circularly permuted yellow fluorescent protein (cpYFP). Cultured chondrocytes or cartilage explants were incubated in media containing interleukin-1 beta (10 ng/ml) or tumor necrosis factor-alpha (10 ng/ml) to stimulate an inflammatory response. Mitochondrial imaging was carried out by confocal and two-photon microscopy. Mitochondrial oxidative status was evaluated by "superoxide flash′′ activity recorded with time lapse scanning.

Results: Cultured chondrocytes contain abundant mitochondria that show active motility and dynamic morphological changes. In intact cartilage, mitochondrial abundance as well as chondrocyte density declines with distance from the surface. Importantly, sudden, bursting superoxide-producing events or "superoxide flashes′′ occur at single-mitochondrion level, accompanied by transient mitochondrial swelling and membrane depolarization. The superoxide flash incidence in quiescent chondrocytes was similar to 4.5 and similar to 0.5 events/1000 mu m(2)* 100 s in vitro and in situ, respectively. Interleukin-1 beta or tumor necrosis factor-alpha stimulated mitochondrial superoxide flash activity by 2-fold in vitro and 5-fold in situ, without altering individual flash properties except for reduction in spatial size due to mitochondrial fragmentation.

Conclusions: The superoxide flash response to proinflammatory cytokine stimulation in vitro and in situ suggests that chondrocyte mitochondria are a significant source of cellular oxidants and are an important previously under-appreciated mediator in inflammatory cartilage diseases.

语种: 英语
所属项目编号: 2013CB531200 ; 2011CB809102 ; 81071474 ; 81171726
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000322361200079
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62716
Appears in Collections:北京大学第三临床医学院_运动医学研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Sports Med, Hosp 3, Beijing 100871, Peoples R China
2.Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Inst Mol Med, Beijing 100871, Peoples R China

Recommended Citation:
Cao, Yongxing,Zhang, Xin,Shang, Wei,et al. Proinflammatory Cytokines Stimulate Mitochondrial Superoxide Flashes in Articular Chondrocytes In Vitro and In Situ[J]. PLOS ONE,2013,8(6).
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