靶向NLRP3炎性小体作为骨关节炎的新治疗靶点。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Inflammopharmacology Pub Date : 2025-01-13 DOI:10.1007/s10787-024-01629-2
Varnita Karmakar, Mayukh Chain, Ankit Majie, Arya Ghosh, Pallav Sengupta, Sulagna Dutta, Papiya Mitra Mazumder, Bapi Gorain
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引用次数: 0

摘要

骨关节炎是最常见的关节炎,是一种与年龄有关的渐进性疾病,其特点是膝关节和髋关节软骨流失和滑膜炎症。基质金属蛋白酶和细胞因子的产生是导致关节疼痛、僵硬和活动明显受限的原因。虽然有多种治疗方法可用于治疗这种疾病,但它们在不同程度上都存在局限性。NLRP3 炎性体由于其失调而在疾病的发展过程中起着至关重要的作用。抑制 NLRP3 炎性体已显示出调节 MMP-13、caspase-1、IL-1β 等物质产生的潜力,这在不同的临床前和临床研究中都得到了积极的反应。为了抑制 NLRP3 炎性体,有几种化合物正处于不同的研究阶段,希望能为骨关节炎的治疗带来新的药物。本综述总结了 NLRP3 激活与骨关节炎发展的机理途径,并讨论了旨在有效治疗骨关节炎的新疗法的进展情况。
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Targeting the NLRP3 inflammasome as a novel therapeutic target for osteoarthritis.

Osteoarthritis, the most common arthritic condition, is an age-related progressive disease characterized by the loss of cartilage and synovial inflammation in the knees and hips. Development of pain, stiffness, and considerably restricted mobility of the joints are responsible for the production of matrix metalloproteinases and cytokines. Although several treatments are available for the management of this disease condition, they possess limitations at different levels. Recently, efforts have focused on regulating the production of the NLRP3 inflammasome, which plays a critical role in the disease's progression due to its dysregulation. Inhibition of NLRP3 inflammasome has shown the potential to modulate the production of MMP-13, caspase-1, IL-1β, etc., which has been reflected by positive responses in different preclinical and clinical studies. Aiming inhibition of this NLRP3 inflammasome, several compounds are in different stages of research owing to bring a novel agent for the treatment of osteoarthritis. This review summarizes the mechanistic pathways linking NLRP3 activation to osteoarthritis development and discusses the progress in new therapeutics aimed at effective treatment.

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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
期刊介绍: Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]
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