Pyroptosis: A Novel Intervention Target in the Progression of Osteoarthritis

Figures & data

Figure 1 Molecular mechanisms of pyroptosis. (A) The canonical inflammasome pathway. (B) The noncanonical inflammasome pathway. (C) The components of inflammasome sensors, adaptors, effectors, and inflammatory precursor molecules in pyroptosis.

Figure 2 Macroscopic pathological changes and microscopic pathogenic relationships in OA joints. (A) Pathological changes in OA joints compared with normal joints. (B) Microscopic pathogenic interactions by cytokines in OA joints.

Table 1 Summary of NLRP3-Associated Inhibitors in Osteoarthritis

Intervention Strategies	Signaling Pathway	Detected Molecules	Biological Function	Reference
Loganin	NF-κB/NLRP3	MMP-3, MMP-13, Cryopyrin, Col II, CD31, Endomucin, Col Ⅹ,	Inhibits cartilage degradation	92
Ursolic acid	NF-κB/NLRP3	MMP-13, IL-1β, IL-6, Col II A 1, NLRP3	Inhibits cartilage degradation	93
Chondroitin sulphate	NF-κB/NLRP3	IL-1β, Pro- IL-1β, Caspase-1, NF-κB	Inhibits cartilage degradation	94
KMU-1170	NF-κB/NLRP3	iNOS, COX-2, IL-1β, TNF-α, IL-6	Inhibits FLS inflammation	95
Amitriptyline	TLR-4, IL-1R/ NF-κB/NLRP3	MMP-1, MMP-3, MMP-9, MMP-13, ADAMTS-4, COX-2, NLRP3, IL-1β	Inhibits chondrocyte degradation	96
Loratadine	Nrf2/NF-κB/NLRP3	ROS, NOX4, TxNIP, NLRP3, ASC, IL-1β, IL-18, Nrf2	Inhibits chondrocyte cellular stress	99
Lico A	Nrf2/HO-1/ NF-κB	NLRP3, GSDMD, Pro-caspase-1, IL-1β, IL-18, Col II, Aggrecan	Inhibits cartilage degradation	100
CY-09	NF-κB/ NLRP3	MMP-13, ADAMTS-5, Aggrecan, Col II, IL-1β, IL-9, IL-18, PGE2, NLRP3, ASC, GSDMD, Caspase-1	Inhibits cartilage degradation	67
Chrysin	NF-κB/ NLRP3	NLRP3, ASC, Caspase-1, IL-1β, IL-18,	Inhibits synovial inflammation and OA pain	101
Baicalein	NF-κB/ NLRP3	MMP-13, ADAMTS-5, Col II, NLRP3, Caspase-1, IL-1β, TNF-α	Inhibits cartilage degradation	63
Less mechanical loading	NF-κB/ NLRP3	MMP-3, MMP-13, ADAMTS-5, NLRP3, IL-1β, Caspase-1, iNOS, COX-2	Inhibits cartilage degradation, subchondral bone remodeling, and inflammation	62

Abbreviations: MMP, matrix metalloproteinase; Col, collagen; iNOS, inducible nitric oxide synthase; COX-2, cyclooxygenase-2; FLS, fibroblast-like synoviocyte; ADAMTS, a disintegrin and metalloproteinase with a thrombospondin type 1 motifs; ROS, reactive oxygen species; NOX4, nicotinamide adenine dinucleotide phosphate 4; TxNIP, thioredoxin-interacting protein; Nrf2, NF-E2-related factor 2; PGE2, Prostaglandin E2.