Karmakar Varnita, Chain Mayukh, Majie Ankit, Ghosh Arya, Sengupta Pallav, Dutta Sulagna, Mazumder Papiya Mitra, Gorain Bapi
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India.
Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, United Arab Emirates.
Inflammopharmacology. 2025 Feb;33(2):461-484. doi: 10.1007/s10787-024-01629-2. Epub 2025 Jan 13.
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.
骨关节炎是最常见的关节炎病症，是一种与年龄相关的渐进性疾病，其特征是膝关节和髋关节的软骨丢失和滑膜炎症。疼痛、僵硬以及关节活动度的显著受限会导致基质金属蛋白酶和细胞因子的产生。尽管有几种治疗方法可用于管理这种疾病状况，但它们在不同层面都存在局限性。最近，研究重点已集中在调节NLRP3炎性小体的产生上，由于其失调，NLRP3炎性小体在该疾病的进展中起关键作用。抑制NLRP3炎性小体已显示出调节MMP - 13、半胱天冬酶 - 1、白细胞介素 - 1β等产生的潜力，这在不同的临床前和临床研究中的阳性反应中得到了体现。为了抑制这种NLRP3炎性小体，由于有望带来一种治疗骨关节炎的新型药物，几种化合物正处于不同的研究阶段。本综述总结了将NLRP3激活与骨关节炎发展联系起来的机制途径，并讨论了旨在有效治疗的新疗法的进展。
