Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation.
Pathophysiology of osteoarthritis: canonical NF-κB/IKKβ-dependent and kinase-independent effects of IKKα in cartilage degradation and chondrocyte differentiation.
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DOI：
10.1136/rmdopen-2015-000061
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发表时间：
2015
期刊：
影响因子：
6.2
通讯作者：
Goldring MB
中科院分区：
文献类型：
--
作者：
Olivotto E;Otero M;Marcu KB;Goldring MB
骨关节炎（OA）是一种由异常生物力学和随之而来的细胞源性和组织源性因素驱动的全关节疾病，是一种患病率最高的风湿性疾病，造成严重的健康负担，并产生巨大的经济影响。核因子 κB (NF-κB) 家族的成员协调机械、炎症和氧化应激激活过程，因此代表了 OA 疾病的潜在治疗靶点。两种关键激酶 IκB 激酶 (IKK) α 和 IKKβ 激活 NF-κB 二聚体，这些二聚体可能转位至细胞核并调节参与细胞外基质重塑和软骨细胞终末分化的特定靶基因的表达。 IKKα 是激活所谓的非经典途径所需的，在体内和体外具有许多不依赖 NF-κB 和不依赖激酶的功能，包括控制软骨细胞肥大分化和胶原酶活性。在这篇简短的综述中，我们将讨论 NF-κB 信号传导在 OA 病理学中的作用，重点是 IKKα 独立于其激酶活性和 NF-κB 激活的功能作用。
Osteoarthritis (OA), a whole-joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors, is a rheumatic disease with the highest prevalence, representing a severe health burden with a tremendous economic impact. Members of the nuclear factor κB (NF-κB) family orchestrate mechanical, inflammatory and oxidative stress-activated processes, thus representing a potential therapeutic target in OA disease. The two pivotal kinases, IκB kinase (IKK) α and IKKβ, activate NF-κB dimers that might translocate to the nucleus and regulate the expression of specific target genes involved in extracellular matrix remodelling and terminal differentiation of chondrocytes. IKKα, required for the activation of the so-called non-canonical pathway, has a number of NF-κB-independent and kinase-independent functions in vivo and in vitro, including controlling chondrocyte hypertrophic differentiation and collagenase activity. In this short review, we will discuss the role of NF-κB signalling in OA pathology, with emphasis on the functional effects of IKKα that are independent of its kinase activity and NF-κB activation.