These results together with their previous reports that overexpression of SOCS3 or dominant negative STAT3 in joints effectively ameliorated CIA models (30) indicate that IL-6–STAT3–mediated cytokine amplification loop plays a key role in promoting sustained inflammation and joint destruction during arthritis, and this loop can be negatively regulated by SOCS3. This evidence concerns the gene SOCS3 and arthritic joint disease.