Yokota K, Sato K, Miyazaki T, et al. - The present study was conducted to verify the characterization and function of human tumor necrosis factor (TNF) and IL-6–induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. For this analysis, peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was assessed. Researchers analyzed expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3. They further evaluated the effects of NFAT inhibitor and JAK inhibitor. They also explored the association between the number of TNF and IL-6–induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells in patients with RA and the modified total Sharp score or whole-body bone mineral density). The findings illustrate that TNF and IL-6–induced osteoclasts may contribute to the pathology of inflammatory arthritis correlated with joint destruction, such as RA.