Involvement of ERCC1 in the pathogenesis of osteoarthritis through the modulation of apoptosis and cellular senescence.
Involvement of ERCC1 in the pathogenesis of osteoarthritis through the modulation of apoptosis and cellular senescence.
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ERCC1 通过调节细胞凋亡和细胞衰老参与骨关节炎的发病机制。
DOI：
10.1002/jor.22656
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发表时间：
2014-10
影响因子：
2.8
通讯作者：
Huard, Johnny
中科院分区：
文献类型：
--
作者：
Takayama, Koji;Kawakami, Yohei;Lee, Sahnghoon;Greco, Nick;Lavasani, Mitra;Mifune, Yutaka;Cummins, James H.;Yurube, Takashi;Kuroda, Ryosuke;Kurosaka, Masahiro;Fu, Freddie H.;Huard, Johnny
DNA损伤是与年龄相关的病理的一个原因，包括骨关节炎（OA）。切除修复交叉互补组1 （ERCC1）是DNA损伤修复所必需的内切酶。在这项研究中，我们研究了ERCC1在软骨细胞中的功能及其与OA病理生理的关系。评估正常软骨和骨关节炎软骨中ERCC1的表达，以及分解代谢应激下软骨细胞中ERCC1表达的变化。在白细胞介素-1β刺激下，使用小干扰RNA （siRNA）抑制软骨细胞中的ERCC1也被评估。最后，研究细胞衰老和凋亡与ERCC1功能的关系。ERCC1的表达在暴露于白细胞介素(IL)-1β后4小时内升高，12小时后下降。siRNA抑制ERCC1增加了基质金属肽酶13的表达，减少了II型胶原的表达。ERCC1抑制也增加了凋亡细胞和衰老细胞的数量。软骨细胞中ERCC1的抑制增加了OA相关蛋白的表达、凋亡、细胞衰老和肥大样变化，这表明ERCC1对保护人类软骨细胞（hc）免受分解代谢应激至关重要，并为OA的病理生理学和治疗提供了潜在的靶点。
DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment.
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DOI：
10.1073/pnas.1531903100
发表时间：
2003-07-22
影响因子：
11.1
作者：
Kiecolt-Glaser, JK;Preacher, KJ;Glaser, R
通讯作者：
Glaser, R
影响因子：
7.8
作者：
Price, JS;Waters, JG;Clark, IM
通讯作者：
Clark, IM
影响因子：
3.3
作者：
Dunkern, TR;Kaina, B
通讯作者：
Kaina, B
DOI：
10.1083/jcb.201009094
发表时间：
2011-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rodier F;Campisi J
通讯作者：
Campisi J
影响因子：
7
作者：
Lopez-Armada, M. J.;Carames, B.;Blanco, F. J.
通讯作者：
Blanco, F. J.