Table 1.

Adipokines implicated in rheumatoid arthritis and osteoarthritis.

Stimulation	Target Factors		Effects in Tissue	Disease	Receptor	Known Pathways	References
Adiponectin
	IL-6	↑	FLSs	OA & RA	AdipoR1	AMPK/p38/IKKαβ and NF-κB	[26]
	VEGF, MMPs	↑	FLSs	RA	N/A	N/A	[27]
	IL-6, RANTES, MMP-3	↑	FLSs, lymphocytes, endothelial cells, and chondrocytes	RA	N/A	PKA/NF-κB/p38MAPK/PKC	[29]
	PGE2	↑	FLSs	RA	AdipoR1	NF-κB	[30,31]
	OSM	↑	Osteoblasts	RA	N/A	PI3K/Akt and NF-κB	[33]
	IL-6, IL-8, and CCL2	↑	Osteoblasts and chondrocytes	OA	N/A	p38/MAPK	[40]
	IL-6, MMP-1,-3	↑	Chondrocytes	OA	N/A	p38/ERK1/2/JNK	[41]
	ICAM-1	↑	FLSs	OA	AdipoR1	LKB1, CaMKII, AMPK, and AP-1	[42]
	VCAM-1	↑	Chondrocytes	RA & OA	N/A	JAK2 and PI3K	[63]
Leptin
	MMP-13	↑	Chondrocytes	OA	N/A		[50]
	IL-1β, MMP-9 and MMP-13	↑	Chondrocytes	OA	OBRb		[53]
	IL-8	↑	FLSs	RA & OA	OBRI	JAK2/STAT3 and IRS1/PI3K/Akt/NF-κB	[61]
	IL-6	↑	FLSs	OA	OBRI	IRS-1/PI3K/Akt, and AP-1	[62]
	VCAM-1	↑	Chondrocytes	RA & OA	N/A	JAK2 and PI3K	[63]
	ADAMTS-4, -5 and -9	↑	Chondrocytes	OA	N/A	MAPK and NF-κB	[64]
	IL-6	↑	FLSs	RA	OBRb	JAK2/STAT3	[65]
	OSM	↑	Osteoblasts	RA	OBRI	AKT/miR-93	[66]
Resistin
	CXCL8, CCL2 and IL-6	↑	FLSs	RA	N/A	CAP1	[67]
	VEGF	↑	EPCs	RA	N/A	PKC-δ/AMPK/miR-206	[68]
Visfatin
	IL-6 and IL-8, CCL2 and MMP-3	↑	FLSs	RA	N/A	p38 pathway	[69]
	IGF-1	↓	Chondrocytes	OA	IGF-1R	ERK/MAPK signaling pathway	[70]
	IL-6 and TNF-α	↑	FLSs	OA	N/A	ERK/p38/JNK and miR-199a-5p	[71]
	MMP-3, -12, and -13	↑	Chondrocytes	OA	N/A	HIF-2a	[72]
Other adipokines
	MMP-1, -3 and -9, ADAMTS-4 and -5, IL-1β		Chondrocytes	OA	N/A	JNK, ERK and MAPK	[73]

IL-6, interleukin 6; FLSs, fibroblast-like synoviocytes; OA, osteoarthritis; RA, rheumatoid arthritis; AdiopoR1, adiponectin receptor 1; AMPK, AMP-activated protein kinase; IKKα/β, IκB kinase alpha/beta; NF-κB, nuclear factor-kappa B; VEGF, vascular endothelial growth factor; MMP, matrix metalloproteinase; RANTES, regulated upon activation, normal T cells expressed and secreted; PKA, protein kinase A; p38MAPK, P38 mitogen-activated protein kinase; PKC, protein kinase C; PGE2, prostaglandin E2; OSM, oncostatin M; PI3K, phosphatidylinositol 3 kinase; IL-8, interleukin-8; CCL2, chemokine (C-C motif) ligand 2; ERK1/2, extracellular signal-regulated protein kinases 1 and 2; JNK, c-Jun N-terminal kinase; ICAM-1, intercellular adhesion molecule 1; LKB1, liver kinase B1; CaMKII, Ca²⁺/calmodulin-dependent protein kinase II; AP-1, activator protein 1; VCAM-1, vascular cell adhesion molecule 1; JAK2, Janus kinase 2; IL-1β, interleukin-1 beta; OBRb and OBRl, long isoform of leptin receptor; STAT3, signal transducer and activator of transcription 3; IRS1, insulin receptor substrate-1; ADAMTS-4, ADAM metallopeptidase with thrombospondin type 1 motif 4; ADAMTS-5, ADAM metallopeptidase with thrombospondin type 1 motif 5; ADAMTS-9, ADAM metallopeptidase with thrombospondin type 1 motif 9; miR, microRNA; CXCL8, C-X-C motif chemokine ligand 8; CAP1, adenylate cyclase-associated protein 1; EPCs, endothelial progenitor cells; IGF-1, insulin-like growth factor 1; IGF-1R, IGF-1 receptor; TNF-α, tumor necrosis factor alpha; HIF-2α, hypoxia-inducible factor 2 alpha.