Inflammation and intracellular metabolism: new targets in OA.
Inflammation and intracellular metabolism: new targets in OA.
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DOI：
10.1016/j.joca.2014.12.016
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发表时间：
2015-11
影响因子：
7
通讯作者：
Liu-Bryan R
中科院分区：
文献类型：
--
作者：
Liu-Bryan R
关节软骨变性是骨关节炎（OA）的标志。关节轻度慢性炎症可促进骨性关节炎进展。新出现的证据表明，生物能量传感器将代谢与炎症结合起来，以改变生理和临床表型。细胞生物能量代谢的变化可以重新编程炎症反应，炎症可以破坏细胞能量平衡，增加细胞应激。amp活化蛋白激酶（AMPK）和sirtuin 1 （SIRT1）是两个关键的生物能量传感器，在细胞和全身水平上调节能量平衡。AMPK和SIRT1的失调与多种人类疾病和衰老有关。本文综述了AMPK和SIRT1在关节组织稳态和骨性关节炎中的作用的最新发现，重点关注关节软骨细胞中的AMPK和SIRT1如何在应激反应（如炎症反应）中调节细胞内能量代谢，以及这些变化如何决定特定效应物的功能，并讨论了AMPK和SIRT1作为骨性关节炎新治疗靶点的翻译意义。
Articular cartilage degeneration is hallmark of osteoarthritis (OA). Low-grade chronic inflammation in the joint can promote OA progression. Emerging evidence indicates that bioenergy sensors couple metabolism with inflammation to switch physiological and clinical phenotypes. Changes in cellular bioenergy metabolism can reprogram inflammatory responses, and inflammation can disturb cellular energy balance and increase cell stress. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are two critical bioenergy sensors that regulate energy balance at both cellular and whole-body levels. Dysregulation of AMPK and SIRT1 has been implicated in diverse human diseases and aging. This review reveals recent findings on the role of AMPK and SIRT1 in joint tissue homeostasis and OA, with a focus on how AMPK and SIRT1 in articular chondrocytes modulate intracellular energy metabolism during stress responses (e.g., inflammatory responses) and how these changes dictate specific effector functions, and discusses translational significance of AMPK and SIRT1 as new therapeutic targets for OA.