NOS2 and osteoarthritis: It appears that, at the AdipoR1 level, from both the chondrocytes and the osteoarthritis synovial fibroblasts (OASFs), high adiponectin levels stimulate via the AMPK and nuclear factor (NF-κB) signaling pathways for the release of pro-inflammatory interleukins (such as IL-6), matrix metalloproteases (MMP-1 and -3), and the production of inducible nitric oxide synthase (iNOS), generating pain, inflammation, and matrix degradation [24,25].