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首页> 外文期刊>Biochemical Pharmacology >Targeting chronic innate inflammatory pathways, the main road to prevention of osteoarthritis progression
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Targeting chronic innate inflammatory pathways, the main road to prevention of osteoarthritis progression

机译：靶向慢性天生的炎症途径，主要是预防骨关节炎进展的主要道路

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Osteoarthritis (OA) is a chronic joint disease characterized by cartilage degradation, osteophyte formation, subchondral bone sclerosis, and synovitis. Systemic factors such as obesity and the components of the metabolic syndrome seem to contribute to its progression. Breakdown of cartilage ensues from an altered balance between mechanical overload and its absorption by this tissue. There is in this context a status of persistent local inflammation by means of the chronic activation of innate immunity. A broad variety of danger-associated molecular patterns inside OA joint are able to activate pattern recognition receptors, mainly TLR (toll-like receptor) 2 and 4, which are overexpressed in the OA cartilage. Chronic activation of innate inunune responses in chondrocytes results in a robust production of pro-inflammatory cytokines and chemokines, as well as of tissue destructive enzymes, downstream of NF-kappa B and MAPK (mitogen activated protein kinase) dependent pathways. Besides, the toxic effects of an excess of glucose and/or fatty acids, which share the same pro-inflammatory intracellular signalling pathways, may add fuel to the fire. Not only high concentrations of glucose can render cells prone to inflammation, but also AGEs (advanced glycation end products) are integrated into the TLR signalling network through their own innate immune receptors. Considering these mechanisms, we argue for the control of both primary inflammation and proteolytic catabolism as a preventive strategy in OA, instead of focusing treatment on the enhancement of anabolic responses. Even though this approach would not return to normal already degraded cartilage, it nonetheless might avoid damage extension to the surrounding tissue.
机译：骨关节炎（OA）是一种慢性关节疾病，其特征在于软骨降解，骨赘，骨赘，骨髓性骨硬化和滑膜炎。肥胖症等系统因素和代谢综合征的组分似乎有助于其进展。软骨细分随着机械过载与该组织的吸收之间的改变的平衡。在这种情况下，通过先天免疫的慢性激活，通过慢性激活持续局部炎症的状态。在OA关节内部具有众多危险相关的分子模式能够激活图案识别受体，主要是TLR（Toll样受体）2和4，其在OA软骨中过度表达。慢性激活软骨细胞中的急性急性反应导致促进的促炎细胞因子和趋化因子以及组织破坏性酶，NF-Kappa B和MAPK（促丝糖原活化蛋白激酶）依赖性途径的促进生产。此外，葡萄糖和/或脂肪酸过量的毒性作用，其共享相同的促炎细胞内信号通路，可以将燃料添加到火中。不仅高浓度的葡萄糖可以使细胞容易发生炎症，而且还通过自己的先天免疫受体集成到TLR信令网络中的年龄（晚期糖化终端产品）。考虑到这些机制，我们争辩于控制原发性炎症和蛋白水解酵素分解代谢作为OA的预防策略，而不是重点关注有组织反应的增强。尽管这种方法不会恢复正常已经降级的软骨，但它仍然可能避免损坏围绕周围组织。

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