Ageing and the pathogenesis of osteoarthritis.
Ageing and the pathogenesis of osteoarthritis.
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DOI：
10.1038/nrrheum.2016.65
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Diekman BO
中科院分区：
文献类型：
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作者：
Loeser RF;Collins JA;Diekman BO
影响关节组织的骨关节炎相关变化促进骨关节炎（OA）的发展。虽然老龄化和OA密切相关，但它们是独立的过程。已经阐明了衰老导致OA的几种潜在机制。本文综述了以下因素的作用：年龄相关性炎症（也称为“炎症”）;细胞衰老（包括衰老相关分泌表型（SASP））;线粒体功能障碍和氧化应激;由于5′-AMP活化蛋白激酶（AMPK）活性降低导致的能量代谢功能障碍，这与减少的自噬有关;以及由于细胞外基质中与年龄相关的变化而引起的细胞信号传导的改变。这些不同的过程通过促进促炎、分解代谢状态并伴随对细胞死亡的易感性增加而促进OA的发展，这些过程共同导致关节组织破坏增加和受损基质的修复缺陷。迄今为止，大多数研究都集中在关节软骨上，确定其他关节组织中是否存在类似的机制将非常重要。对促进OA的衰老相关机制的更好理解可能会导致发现新的治疗靶点，旨在减缓或阻止这种慢性和致残性疾病的进展。虽然与衰老相关的变化促进了骨关节炎（OA）的发展，但衰老和OA是独立的过程。在这篇综述中，作者讨论了年龄相关因素通过对关节软骨的影响导致OA的机制，并提出未来我们对这些机制的理解将为减缓或阻止OA进展的新疗法提供信息。
Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as ‘inflammaging’); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5′-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition. Although changes associated with ageing promote the development of osteoarthritis (OA), ageing and OA are independent processes. In this Review, the authors discuss the mechanisms by which age-related factors contribute to OA through effects on articular cartilage and propose that future improvements in our understanding of these mechanisms will inform new therapies to slow or stop the progression of OA.