Adipokine Contribution to the Pathogenesis of Osteoarthritis

Table 1

Effects of adipokines on OA pathogenesis.

	Cartilage	Bone	Proteases	Cytokines	Inflammation
Leptin	↓ chondrocyte proliferation; ↓ proteoglycan synthesis; ↑ type I collagen synthesis	↑ osteoblast proliferation; ↑ ossification; ↑ alkaline phosphatase; ↑ osteocalcin	↑ MMP1, MMP-13; ↑ MMP3, MMP2/9; ↑ ADAMTS-4, ADAMTS-5, ADAMTS-9; ↑ cysteine proteases	↑ IL-1β, IL-6; ↑ TNF-α, TGF-β1, IGF-1; ↑ IL-8, GRO, MCP1; ↓ FGF	↑ NOS2, iNOS; ↑ PGE2, COX-2; ↑ uCTX-II; ↑ sCOMP
Adiponectin	↑ chondrocyte proliferation; ↑ proteoglycan synthesis; ↑ type II collagen synthesis; ↓ matrix mineralization	↑ osteoblast proliferation; ↑ osteoclast differentiation; ↑ RANKL; ↓ OPG	↑ MMP1; ↑ MMP3, MMP2/9; ↑ TIMP1, TIMP2; ↓ MMP13	↓ IL-1β, IL-6; ↓ IL-8, MCP1, CCL2; ↓ VEGF	↓ NOS2, iNOS; ↓ PGE2; ↓ uCTX-II, sCOMP; ↓ VCAM-1, ICAM-1
Resistin	↓ proteoglycan synthesis; ↓ type II collagen synthesis	↑ osteoblast proliferation; ↑ osteoclast differentiation	↑ MMP1, MMP-13; ↑ ADAMTS-4	↑ IL-1β, IL-6; ↑ TNF-α; ↑ CCL2, CX3CL1; ↑ BMP2	↑ PGE2; ↑ hsCRP
Visfatin	↓ chondrocyte phenotype; ↓ proteoglycan synthesis; ↓ type II collagen synthesis	↑ osteoblast proliferation; ↓ osteoclast differentiation	↑ MMP-13; ↑ MMP3; ↑ ADAMTS-5	↑ IL-1β, IL-6; ↑ TNF-α; ↑ IL-8, MCP1; ↑ NGF	↑ NO; ↑ PGE2, hsCRP; ↑ uCTX-II; ↑ AGG1/AGG2

ADAMTS: a disintegrin and metalloproteinase with thrombospondin motifs; AGG: aggrecan; BMP: bone morphogenetic protein; CCL2: chemokine C-C motif ligand 2; COMP: cartilage oligomeric matrix protein; COX-2: cyclooxygenase-2; CX3CL1: chemokine (C-X3-C motif) ligand 1; FGF: fibroblast growth factor; GRO: growth-related oncogene; hsCRP: high-sensitivity C-reactive protein; ICAM-1: intercellular adhesion molecule-1; IGF-1: insulin-like growth factor-1; IL: interleukin; iNOS: inducible nitric oxide synthase; MCP-1: monocyte chemoattractant protein-1; MMP: metalloproteinases; NGF: neuronal growth factor; NO: nitric oxide; NOS2: type 2 nitric oxide synthase; OPG: osteoprotegerin; PGE₂: prostaglandin E₂; RANKL: receptor activator of nuclear factor-kappa B ligand; sCOMP: synovial cartilage oligomeric matrix protein; TIMP: tissue inhibitor of metalloproteinases; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-alpha; uCTXII: urine C terminal telopeptide of type II collagen; VCAM-1: vascular cell adhesion molecule-1; VEGF: vascular endothelial growth factor.