Mechanism of hyaluronan depolymerization due to Reactive oxygen species (ROS) produced by synoviocytes cultured in hypoxia, resulting synovial proliferation.

缺氧培养的滑膜细胞产生活性氧（ROS）导致透明质酸解聚，导致滑膜增殖的机制。

• 批准号: 14571411
• 负责人: AKAGI Masao
• 金额: $ 2.24万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571411/
• 关键词: Osteoarthrosis; Synovium; Cartilage; Hyaluronan; Depolymerization; Mechanical stress; Reactive oxygen species; 分子量; フリーラジカル; 過酸化物質; スーパーオキサイドディスムターゼ; 軟骨保護作用; Superoxidedismutase; ヒアルロン酸合成酵素; 関節炎; 活性酸素種; 阻血再潅流

Etiology of osteoarthritis is supposed to involve cartilage degeneration and synovial proliferation. We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (NA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action. ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument (FX-3000). Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity, catalysing the dismutation of superoxide anion into hydrogen peroxide, and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively. ROS depolymerized HA molecules. Cyclic tensile strech depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress. These data suggest that ROS play an important role in mechanical stress-induced HA depolymerization. Depolymerized HA may stimulate synovial proliferation and activate synovial inflammation.

骨关节炎的病因应该涉及软骨变性和滑膜增殖。我们以前已经证明，活性氧（ROS）与软骨降解有关。关节炎患者据报道，透明质酸（NA）的大小降低，是滑液中主要的大分子的大小（NA）。这项研究的目的是确定HA的分子量范围的改变，结果是在软骨细胞上加载的机械变形，以及ROS参与此作用。 ROS是通过黄嘌呤氧化酶对低黄嘌呤氧化产生的。使用真空操作仪器（FX-3000）加载环状拉伸拉伸。使用三明治酶结合测定法测量HA水平。超氧化物歧化酶（SOD）活性，分别使用水溶性四唑和化学发光探针测量了超氧化阴离子在过氧化氢中的损坏和ROS。 ROS解聚HA分子。循环拉伸链链杆菌解聚HA并诱导ROS。 SOD不仅抑制了ROS诱导，还抑制了由机械应力引起的HA解聚化。这些数据表明，ROS在机械应力诱导的HA解聚中起着重要作用。解聚HA可能会刺激滑膜增殖并激活滑膜炎症。

项目成果

Reactive oxygen species depolymerize hyaluronan : involvement of the hydroxyl redical.

活性氧使透明质酸解聚：羟基自由基的参与。

• 发表时间: 2003
• 期刊: Pathophysiology. 9
• 作者: Yamazaki K;et al.
• 通讯作者: et al.

Yamazaki K, et al.: "Reactive oxygen species depolymerize hyaluronan : involvement of the hydroxylradical."Pathophysiology. 9・47. 215-220 (2003)

Yamazaki K 等人：“活性氧解聚透明质酸：羟基自由基的参与”，9·47（2003）。

Reactive oxygen species depolymerize hyaluronan : involvement of the hydroxyl radical.

活性氧使透明质酸解聚：羟基自由基的参与。

• 发表时间: 2003
• 期刊: Pathophysiology 9
• 作者: Yamazaki K;et al.
• 通讯作者: et al.

山崎顕二: "軟骨細胞に対する機械的ストレスのヒアルロン酸に対する影響:ヒドロキシラジカルの影響について"近大医学会雑誌. 26巻3号. 113-124 (2002)

Kenji Yamazaki：“软骨细胞的机械应力对透明质酸的影响：羟基自由基的影响”近代大学医学会杂志，第 26 卷，第 3 期。113-124（2002 年）。