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损伤相关分子模式(DAMPs)作为治疗骨关节炎的潜在靶点:文献综述视角

The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature.

作者信息

Lambert Cécile, Zappia Jérémie, Sanchez Christelle, Florin Antoine, Dubuc Jean-Emile, Henrotin Yves

机构信息

MusculoSKeletal Innovative Research Lab, University of Liège, Institute of Pathology, CHU Sart-Tilman, Liège, Belgium.

Orthopaedic Department, University Clinics St. Luc, Brussels, Belgium.

出版信息

Front Med (Lausanne). 2021 Jan 18;7:607186. doi: 10.3389/fmed.2020.607186. eCollection 2020.

Abstract

During the osteoarthritis (OA) process, activation of immune systems, whether innate or adaptive, is strongly associated with low-grade systemic inflammation. This process is initiated and driven in the synovial membrane, especially by synovium cells, themselves previously activated by damage-associated molecular patterns (DAMPs) released during cartilage degradation. These fragments exert their biological activities through pattern recognition receptors (PRRs) that, as a consequence, induce the activation of signaling pathways and beyond the release of inflammatory mediators, the latter contributing to the vicious cycle between cartilage and synovial membrane. The primary endpoint of this review is to provide the reader with an overview of these many molecules categorized as DAMPs and the contribution of the latter to the pathophysiology of OA. We will also discuss the different strategies to control their effects. We are convinced that a better understanding of DAMPs, their receptors, and associated pathological mechanisms represents a decisive issue for degenerative joint diseases such as OA.

摘要

在骨关节炎(OA)进程中,免疫系统的激活,无论是先天性免疫还是适应性免疫,都与低度全身炎症密切相关。这一过程在滑膜中启动并由其驱动,特别是滑膜细胞,这些细胞自身先前已被软骨降解过程中释放的损伤相关分子模式(DAMPs)激活。这些片段通过模式识别受体(PRRs)发挥其生物学活性,进而诱导信号通路的激活,除了释放炎症介质外,后者还促成了软骨与滑膜之间的恶性循环。本综述的主要目的是向读者概述这些被归类为DAMPs的众多分子,以及它们对OA病理生理学的影响。我们还将讨论控制其作用的不同策略。我们深信,更好地理解DAMPs、它们的受体以及相关病理机制,对于诸如OA等退行性关节疾病而言是一个决定性问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9035/7847938/6f7429a72cf7/fmed-07-607186-g0001.jpg

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