Table 1

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

OriginsFactorsEffectsReferences
Bone resorptionTGF-β1Induce endothelial progenitor cell and osteoprogenitor migration and chondrocyte hypertrophy and apoptosis 42 60 70
IGF-1Induce chondrocyte anabolism and prevent chondrocyte maturation and apoptosis 71–73
Ca-PiInduce chondrocyte catabolism 74
PreosteoclastPDGF-BBModulate chondrocytes through abnormal angiogenesis 61
Exosomal let-7a-5pPromote the hypertrophic differentiation of chondrocytes by targeting Smad2 75
Mature osteoclastExosomal let-7a-5pPromote the hypertrophic differentiation of chondrocytes by targeting Smad2 75
Type H endothelial cellMMP-9,
RANKL
Stimulate osteoclast migration to indirectly affect chondrocytes 56
Mature osteoblastIL-6, PGE2Enhance osteoclast formation to indirectly regulate chondrocytes 43–45
VEGFStimulate angiogenesis and osteoclast recruitment to indirectly affect chondrocytes 46 47
RANKLStimulate osteoclast recruitment and differentiation to indirectly regulate chondrocytes 46 47
MMP-9Promote osteoclast recruitment to indirectly affect chondrocytes 43
SLIT3,
TGF-β1
Induce subchondral angiogenesis to indirectly affect chondrocytes 57–59
OsteocyteVEGF,
TGF-β1
Stimulate angiogenesis to indirectly regulate chondrocytes 33 34 41
RANKLInduce osteoclast recruitment and differentiation to indirectly modulate chondrocytes 33 34
Hypertrophic chondrocyteIL-1β,
IL-6,
TNF-α
Induce osteoclast differentiation directly or indirectly 76–81
RANKL, VEGFInduce osteoclast chemotaxis and differentiation 82 83
HMGB1Promote osteoclast recruitment to indirectly affect chondrocytes 84 85
Senescent chondrocyteSASPPromote osteoclast chemotaxis and differentiation 86 87
Apoptotic chondrocyteCXCL12Enhance osteoclast recruitment and differentiation 91–93
Necrotic chondrocyteDAMPsPromote osteoclast formation 94 95