Adipokine Contribution to the Pathogenesis of Osteoarthritis

Figure 6

Visfatin signaling. Visfatin stimulates monocytes to release IL-6. IL-6 signals increase the expression level of STAT3 which upregulates the active enzymatic form of visfatin/PBEF/Nampt. Visfatin/PBEF/Nampt can increase cell survival through Sirt-1 and Sirt-6 stimulating the release of TNF-α inducing a chronic low grade inflammation. In the second pathway, visfatin signals through the cells surface receptor β1 integrin. This binding upregulates and activates p38 MAPK and ERK1/2. The MAPK cascade increases the expression of AP-1 and NF-kB that upregulate SDF-1, leading to increased survival and migration. The third pathway was demonstrated through the activation of unknown receptor increasing the antioxidative enzymes superoxide dismutase (SOD) and catalase (CAT).