Table 1 List of drugs inhibiting subchondral osteoclast differentiation and maturation

Agent	Target	Signaling pathway	Function	Ref.
Metformin	BMMs	AMPK/NF-κB/ERK signaling	Inhibition osteoclast formation	[151]
Diterbutyl phthalate	BMMs/RAW264.7	ERK/c-fos/NFATc1 signaling	Inhibition of subchondral osteoclast formation and related angiogenesis and neurogenesis	[152]
Dihydroartemisinin	Osteoclast precursors	NF-κB/MAPK/NFATc1 signaling	Inhibition of osteoclast formation and bone resorption in the early stage of OA	[109]
Halofuginone	BMMs	Smad2/3-dependent TGF-β signaling	Inhibition of osteoclast bone resorption	[153]
Neratinib	ATDC5 cells/BMMs	MAPK/NF-κB signaling	Protect cartilage and inhibit osteoclast formation	[154]
Paroxetine	ATDC5 cells/BMMs	NF-κB signaling	Inhibition of pyrosis and osteoclast formation	[155]
Total lignans	BMMs	ERK/NFATc1 signaling	Inhibition of osteoclast differentiation	[156]
PP121	BMMs	RANKL/Src/MAPK/Akt signaling	Inhibition of osteoclast formation and bone resorption	[157]
Isorhamnetin	ATDC5 cells/BMMs	RANKL/ MAPK/ NF-κB signaling	Inhibit osteoclast formation and protect chondrocytes by regulating ROS homeostasis	[158]
Nirogacestat	BMMs	RANKL/NFATc1 signaling	Inhibition of osteoclast formation and bone resorption	[159]
USP13	BMMs	AKT/ NF-κB signaling	Inhibition of osteoclastogenesis and osteoclast related gene expression	[160]
Ruboxistaurin	BMMs	PKCδ/MAPKs signaling	Inhibition of osteoclast formation and absorption activity	[161]
Curcuminoid	RAW264.7	RANKL/OPG signaling	Reduce osteoclast activity and maintain osteoblast function	[162]
Irisin	ATDC5 cells/BMMs	RANKL/OPG/NF-κB signaling	Inhibition of osteoclast formation	[163]
FICZ	BMMs	RANKL signaling	Inhibit osteoclast differentiation and activity	[164]
Velutin	BMMs	RANKL/p38 signaling	Inhibits osteoclast formation and bone resorption	[165]
Parthenolide		NF-κB signaling	Inhibits osteoclast formation and survival	[166]
Lenalidomide	BMMs	RANKL/NF-κB signaling	Inhibits osteoclast formation and function	[167]
C-176	Osteoclast precursors	NF-κB/NFATc1 signaling	Inhibits osteoclast formation and activation	[168]
AZ-628	ATDC5 cells/BMMs	NF-κB/MAPK signaling	Inhibition of chondrocyte decomposition, osteoclast formation and bone resorption	[169]
Urolithin A	RAW264.7	RANKL/NF-κB signaling	Inhibition of osteoclast differentiation	[170]
HIF-2α inhibitor	BMMs	Akt/MAPK/NF-κB signaling	Inhibition of osteoclast differentiation	[171]
Diallyl disulfide	RAW264.7	RANKL/NF-κB/ NFATc1 signaling	Inhibition of osteoclast formation, fusion and bone resorption	[172]
Tyrosine kinase inhibitor	BMMs	RANKL/ NF-κB/ STAT3 signaling	Inhibition of osteoclast differentiation	[173]
Gypenoside	BMMs	RANKL/NF-κB/AKT/MAPK signaling	Inhibition of osteoclast formation	[174]