Mechanism of NLRP3 inflammasome intervention for synovitis in knee osteoarthritis: A review of TCM intervention

Abstract

Objective: This paper briefly reviews the structure and function of NLRP3 inflammasomes, signaling pathway, relationship with synovitis in KOA, and intervention of traditional Chinese medicine (TCM) in NLRP3 inflammasomes as a means to improve its therapeutic potential and clinical application. Method: Literatures about NLRP3 inflammasomes and synovitis in KOA were reviewed to analyze and discuss. Result: NLRP3 inflammasome can activate NF-κB mediated signal transduction, which in turn causes the expression of proinflammatory cytokines, initiates the innate immune response, and triggers synovitis in KOA. The TCM monomer/active ingredient, decoction, external ointment, and acupuncture regulating NLRP3 inflammasomes are helpful to alleviate synovitis in KOA. Conclusion: The NLRP3 inflammasome plays a significant role in the pathogenesis of synovitis in KOA, TCM intervention targeting the NLRP3 inflammasome can be a novel approach and therapeutic direction for the treatment of synovitis in KOA.

Keywords: NLRP3 inflammasome; knee osteoarthritis; review; synovitis; traditional Chinese medicine.

FIGURE 1

Mechanism of NLRP3 activation requires two signals. The first priming signal is provided through the interaction of PAMPS/DAMPs with TLRs. This initiates NF-κB signaling, which upregulates the production of pro-IL-1β, pro-IL-18, and inactive NLRP3 protein. The second step is an activation signal which causes NLRP3, ASC, and Pro-caspase-1 to come together. Pro-caspase-1 is then converted into active caspase-1, along with NLRP3 and ASC forms the NLRP3 inflammasome complex. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 causing their activation, which converts into IL-1β and IL-18, subsequent release to extracellular. The molecular mechanisms of NLRP3 inflammasome activation mainly include potassium outflow, calcium signaling, lysosomal destruction, mitochondrial dysfunction, and Golgi.