Early diagnosis and targeted intervention based on the pathogenesis of rapidly progressive osteoarthritis of the hip

Table 3 Potential inhibitors for early intervention to rapidly progressive osteoarthritis of the hip

Agents	Targets	Mechanism	Human disease/animal model	Ref.
Small molecule inhibitors
MCC950	NLRP3	Block ASC oligomerization and inhibit inflammation. Reduce synovitis and cartilage erosion by inhibiting NLRP3 and caspase-1 activation	Mice	[97-100]
VX-765	Caspase-1	Ameliorate the severity and progression of synovitis	Mice	[101,102]
Disulfiram	GSDMD	Inhibits pyroptosis and inflammatory cytokine release in both canonical and noncanonical inflammasome pathways	Mice	[103]
Degrasyn	NLRP3/	Inhibits pyroptosis of synovial macrophages	Mice	[104]
	GSDMD
CY-09	NLRP3	Inhibits cartilage degradation	Rats	[105]
Icariin	NLRP3/	Inhibits inflammation and pyroptosis	Rats	[106]
	Caspase-1
Ursolic acid	NF-κB/	Inhibits cartilage degradation	Rats	[91]
	NLRP3
GYY4137	NF-κB/	Inhibits pyroptosis of synovial macrophages	Mice	[92]
	NLRP3
Loganin	NF-κB/	Inhibits cartilage degradation	Mice	[93]
	Caspase-1
Disease-modifying anti-rheumatic drugs
Chloroquine	The second signal of NLRP3 activation	Inhibit Ca2+-activated K+ channels, which leads to impaired inflammasome activation in THP-1 macrophages Inhibit NLRP3 inflammasome activation	RA/mice	[107,108]
Anakinra	IL-1β receptor antagonist	Inhibit the NLRP3 inflammasome downstream cytokine, IL-1β	RA	[109]
IL-18 binding protein	IL-18 antagonist	Reduces Th17 cells, with the resultant inhibition of osteoclastogenesis, and induces osteoblasts formation	RA/mice	[110]
Tofacitinib	NLRP3	Restore the balance of γδTreg/γδT17 cells by inhibiting NLRP3 inflammasome	RA/mice	[96]

ASC: Apoptosis-associated speck-like protein containing a caspase recruitment domain; NLRP3: Nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3; GSDMD: Gasdermin D; NF-κb: Nuclear factor-κB; IL: Interleukin; RA: Rheumatoid arthritis.