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Table 2 Summary of biofunctions of CCLs in OA

From: CC chemokines and receptors in osteoarthritis: new insights and potential targets

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