Targeting the NLRP3 inflammasome as a novel therapeutic target for osteoarthritis.

Abstract

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.