Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets.
Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets.
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DOI：
10.1007/s11010-017-3047-4
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发表时间：
2017-10
影响因子：
4.3
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Rosenberg JH;Rai V;Dilisio MF;Agrawal DK
骨关节炎（OA）是一种慢性疾病，会使关节退化，通常与年龄增长和肥胖有关。成人OA最常见的两个部位是膝关节和髋关节。肥胖对关节的机械应力增加可导致关节软骨降解并释放损伤相关分子模式（DAMP）。这些DAMP参与与核因子-κ B（NF-κ B）相互作用的各种分子途径，并导致炎性细胞因子的转录和基质金属蛋白酶（MMP）的活化，从而逐渐破坏软骨。本文综述了DAMPs（高迁移率族蛋白1（HMGB-1）、晚期糖基化终产物受体（AGEs）、Alarmin蛋白S100A8和S100A9以及硫酸乙酰肝素）在OA发病机制和进展中的相互作用和作用。HMGB-1从受损或坏死的细胞中释放出来，与Toll样受体（TLR）和EGFR相互作用，诱导炎症信号，并作为炎症细胞因子激活先天免疫细胞。它与HMGB-1、晚期糖基化终产物和先天免疫细胞相互作用，增加局部炎症。Alarmin蛋白在细胞损伤后释放，并通过TLR相互作用，以增加局部炎症和软骨降解。硫酸乙酰肝素已被证明可促进HMGB-1与OA的结合，并可能在OA的进展中发挥作用。靶向这些DAMP可能是治疗OA的潜在治疗策略。
Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B (NF-κB) and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases (MMP) that progressively destroy cartilage. This review focuses on the interactions and contribution to the pathogenesis and progression of OA through the DAMPs: high mobility group box 1 (HMGB-1), the receptor for advanced glycation end-products (RAGE), the alarmin proteins S100A8 and S100A9, and heparan sulfate. HMGB-1 is released from damaged or necrotic cells and interacts with toll-like receptors (TLRs) and RAGE to induce inflammatory signals, as well as behave as an inflammatory cytokine to activate innate immune cells. RAGE interacts with HMGB-1, advanced glycation end-products, and innate immune cells to increase local inflammation. The alarmin proteins are released following cell damage and interact through TLRs to increase local inflammation and cartilage degradation. Heparan sulfate has been shown to facilitate the binding of HMGB-1 to RAGE and could play a role in the progression of OA. Targeting these DAMPs may be potential therapeutic strategies for the treatment of OA.
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影响因子：
1.8
作者：
Cucchiarini M;Henrionnet C;Mainard D;Pinzano A;Madry H
通讯作者：
Madry H
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作者：
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通讯作者：
Agrawal DK
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通讯作者：
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作者：
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