Table 1

Role of the ‘osteoclast–chondrocyte crosstalk’ in the pathogenesis of OA

Origins	Factors	Effects	References
Bone resorption	TGF-β1	Induce endothelial progenitor cell and osteoprogenitor migration and chondrocyte hypertrophy and apoptosis	42 60 70
	IGF-1	Induce chondrocyte anabolism and prevent chondrocyte maturation and apoptosis	71–73
	Ca-Pi	Induce chondrocyte catabolism	74
Preosteoclast	PDGF-BB	Modulate chondrocytes through abnormal angiogenesis	61
Preosteoclast	Exosomal let-7a-5p	Promote the hypertrophic differentiation of chondrocytes by targeting Smad2	75
Mature osteoclast	Exosomal let-7a-5p	Promote the hypertrophic differentiation of chondrocytes by targeting Smad2	75
Type H endothelial cell	MMP-9, RANKL	Stimulate osteoclast migration to indirectly affect chondrocytes	56
Mature osteoblast	IL-6, PGE2	Enhance osteoclast formation to indirectly regulate chondrocytes	43–45
	VEGF	Stimulate angiogenesis and osteoclast recruitment to indirectly affect chondrocytes	46 47
	RANKL	Stimulate osteoclast recruitment and differentiation to indirectly regulate chondrocytes	46 47
	MMP-9	Promote osteoclast recruitment to indirectly affect chondrocytes	43
	SLIT3, TGF-β1	Induce subchondral angiogenesis to indirectly affect chondrocytes	57–59
Osteocyte	VEGF, TGF-β1	Stimulate angiogenesis to indirectly regulate chondrocytes	33 34 41
Osteocyte	RANKL	Induce osteoclast recruitment and differentiation to indirectly modulate chondrocytes	33 34
Hypertrophic chondrocyte	IL-1β, IL-6, TNF-α	Induce osteoclast differentiation directly or indirectly	76–81
	RANKL, VEGF	Induce osteoclast chemotaxis and differentiation	82 83
	HMGB1	Promote osteoclast recruitment to indirectly affect chondrocytes	84 85
Senescent chondrocyte	SASP	Promote osteoclast chemotaxis and differentiation	86 87
Apoptotic chondrocyte	CXCL12	Enhance osteoclast recruitment and differentiation	91–93
Necrotic chondrocyte	DAMPs	Promote osteoclast formation	94 95