A crucial feature of OA is the progressive loss of articular cartilage. Cartilage degradation is a result of the increased expression of genes encoding proteolytic enzymes such as metalloproteinases (MMPs) and aggrecanases (AGGs), as well as inflammatory cytokines, nitric oxide (NO) and prostaglandins (PGEs). The secretion of enzymes involved in the degradation of cartilage accompanied by insufficient cartilage repair result in the breakdown of homeostasis and a shift toward catabolic processes. Adipocytokines acting in an autocrine or paracrine manner stimulate chondrocytes in a dual way. One of the first studies on the impact of leptin on cartilage cells revealed that this peptide increases the anabolic activity of chondrocytes by inducing IGF-1 and TGF-β expression at both mRNA and protein levels [
55]. However, further studies have shown contradictory results. Leptin was reported to increase MMP-2, MMP-9, cathepsin D and type II collagen expression in vivo, at both mRNA and protein levels. This peptide also up-regulated ADAMTS-4 and ADAMTS-5 expression, causing proteoglycan depletion from the articular cartilage of rats [
46]. The latest data suggest that leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 gene expression by mitogen-activated protein kinases and NF-ĸB signaling pathways in human chondrocytes, which results in the subsequent increase of inflammatory processes [
56]. Vuolteenaho et al. [
57] showed that leptin enhanced NO synthesis and PGE2, IL-6 and IL-8 secretion in OA cartilage. Berry et al. [
58] found that the presence of the soluble leptin receptor (sOB-Rb) is associated with reduced cartilage synthesis and increased levels of the tissue degradation marker (N-terminal type IIA procollagen propeptide, PIIANP).
Similarly, adiponectin has both a pro- and anti-inflammatory effect on tissues. Acting in vitro, this peptide induced iNOS activity and IL-6, MMP-3, MMP-9 and MCP-1 (monocyte chemattractant protein-1) expression [
40]. In the study of Francin et al. [
59] the adiponectin transcript level was significantly correlated with those encoding prostaglandin E2 and MMP-13. By contrast, Chen et al. [
60] showed the protective effect of adiponectin on articular cartilage by up-regulating the tissue metallo-proteinase inhibitor (TIMP-2) and decreasing IL-1β-mediated MMP-13 expression. In patients with severe OA, higher plasma adiponectin levels were found and their chondrocytes expressed both adiponectin receptors (AdipoR1 and AdipoR2) and AdipoR1 was mainly expressed in the superficial layers of OA cartilage [
40]. Visfatin had a catabolic effect on articular cartilage. Produced by OA chondrocytes it increased MMP-3, MMP-13 as well as ADAMTS-4 and ADAMTS-5 activity in a mouse model [
61]. Yammani and Loeser [
62] demonstrated that, in human cartilage, visfatin inhibited IGF-1 and led to IGF-1-mediated proteoglycan synthesis. Moreover, Hong et al. [
63] suggested that visfatin could alter the expression, of chondrogenic factors such as the sex-determining region Y-box 9 (SOX-9) and type II collagen. In OA patients visfatin SF level positively correlated with the degradation markers of collagen, (CTX-II) and aggrecans (AGG1, AGG2) [
64]. Recent studies show that most articular visfatin derives from synovium, and the activity of visfatin is involved in chondrocyte and osteoblast activation, so targeting this enzymatic activity to disrupt joint tissue interactions may be novel in OA therapy [
65].