Table 2.
Summary of biofunctions of CCLs in OA
| Chemokine | Model type | Function summary |
|---|---|---|
| Biochemical cascades | ||
| CCL2 | In vitro, mice |
Increase VCAM-1 expression Induce MMP-3 secretion Inhibit proteoglycan synthesis Increase collagenase and gelatinase activity |
| CCL3 | In vitro |
Decrease the expression of cartilage-specific genes Increase expression of MMP3, MMP13, ADAMTS-4, and ADAMTS-5 |
| CCL5 | In vitro |
Increase expression of MMP-1, iNOS, and IL-6 Increase GAG release |
| CCL11 | In vitro |
Increase CCR3 and CCR5 expression Increase MMP-3 and MMP-13 expression |
| CCL19 | In vitro | Increase VEGF secretion |
| CCL20 | In vitro |
Increase b-N-acetylhexosaminidase release Increase release of MMP-1, MMP-13, PGE2, GAG fragment, and IL-6 Inhibit collagen type II mRNA expression Stimulate collagen type X mRNA expression |
| CCL21 | In vitro | Induce ECM loss |
| CCL22 | In vitro | Increase secretion of CCL2, TNF-a, IL-1β, IL-6, p-p65, and COX2 |
| CCL25 | In vitro |
Decrease expression of GAG and collagen type II Induce expression of MMP1, MMP3, EGR1, and SOD2 |
| Chondrocyte apoptosis and subchondral bone remodeling | ||
| CCL2 | In vitro, mice | Promote chondrocyte apoptosis while impeding cellular proliferation |
| CCL3 | In vitro, mice | Promote osteoclast formation |
| CCL22 | In vitro | Mediate TNF-α-induced chondrocyte apoptosis |
| Cellular chemotaxis | ||
| CCL2 | In vitro, in vivo, mice |
Recruit monocytes to the OA joint Recruit macrophages to injured DRG Recruit MSCs to the OA joint Induce transcriptome changes in MSCs |
| CCL3 | In vitro, in vivo | Attracted circulating monocytes to the inflamed synovium |
| CCL11 | In vitro, mice | Increase pre-osteoclast migration in vitro |
| CCL19 | In vitro | Promote migration and resorption activity of osteoclasts |
| CCL21 | In vitro |
Promote migration and resorption activity of osteoclasts Recruit MSCs to OA cartilage in rabbit model |
| CCL22 | In vitro | Inhibit mesenchymal progenitors migration |
| CCL25 | In vitro |
Recruit subchondral mesenchymal progenitors Recruit MSCs to OA cartilage |
| CCL27 | In vitro | Inhibit mesenchymal progenitors migration |
| Pain-related behavior | ||
| CCL2 | In vivo, mice |
Contribute to knee hyperalgesia Modulate sensory afferents in the affected DRG |
| CCL17 | In vitro, mice, rat | Induce inflammatory pain mediators |
| CCL22 | Rat | Associated with pain-related behaviors |