Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy.
Targeting inflammasome-dependent mechanisms as an emerging pharmacological approach for osteoarthritis therapy.
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DOI：
10.1016/j.isci.2022.105548
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发表时间：
2022-12-22
期刊：
影响因子：
5.8
通讯作者：
Bhattaram, Pallavi
中科院分区：
文献类型：
--
作者：
Ramirez-Perez, Sergio;Viridiana Reyes-Perez, Itzel;Emilia Martinez-Fernandez, Diana;Alexis Hernandez-Palma, Luis;Bhattaram, Pallavi
由于世界范围内发病率的增加，关节炎疾病引起了巨大的科学兴趣，并构成了重大的社会经济负担。骨关节炎(OA)是最常见的关节炎形式。这是一种腹股沟关节的疾病，其特征是关节软骨的退化和丢失，并伴随着邻近的软骨下骨的改变。慢性未消退的炎症已被认为是导致骨关节炎关节退行性变和疼痛的关键因素。尽管多次尝试治疗干预，但没有针对OA炎症的有效疾病改良剂可供患者使用。炎性小体是已知在几种疾病的炎性病理中发挥关键作用的蛋白质复合体，在过去十年中，它们在OA发病机制中的作用已经变得明显。从这个意义上说，评估炎性小体作为OA致病特征的潜在调节因子的重要作用是相关的。这篇综述将提供关于为什么了解炎性小体激活对于确定有效的骨关节炎疗法至关重要的概述和观点。我们详细阐述了循环系统和滑液中的细胞外介质以及滑膜成纤维细胞和关节软骨细胞内的细胞内激活物在骨关节炎炎症小体发生中的作用。我们进一步讨论了新出现的炎性小体靶向治疗的优点，并推测了炎性小体阻断OA治疗的潜在策略。健康科学；生物科学；生理学
Arthritic diseases have attracted enormous scientific interest because of increased worldwide prevalence and represent a significant socioeconomic burden. Osteoarthritis (OA) is the most prevalent form of arthritis. It is a disorder of the diarthrodial joints, characterized by degeneration and loss of articular cartilage associated with adjacent subchondral bone changes. Chronic and unresolving inflammation has been identified as a critical factor driving joint degeneration and pain in OA. Despite numerous attempts at therapeutic intervention, no effective disease-modifying agents targeting OA inflammation are available to the patients. Inflammasomes are protein complexes known to play a critical role in the inflammatory pathology of several diseases, and their roles in OA pathogenesis have become evident over the last decade. In this sense, it is relevant to evaluate the vital role of inflammasomes as potential modulators of pathogenic features in OA. This review will provide an overview and perspectives on why understanding inflammasome activation is critical for identifying effective OA therapies. We elaborate on the contribution of extracellular mediators from the circulatory system and synovial fluid as well as intracellular activators within the synovial fibroblasts and articular chondrocytes toward invoking the inflammasome in OA. We further discuss the merits of emerging inflammasome targeting therapies and speculate on the potential strategies for inflammasome blockade for OA therapy. Health sciences; Biological sciences; Physiology
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作者：
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