Finally, using this model, Brines et al. (120) demonstrated that hemeoxygenase-1 (HO-1) deficiency aggravates arthritis progression with local upregulation of pro-inflammatory IL-6 and MMP-3 cytokines and serum RANKL and osteocalcin levels, suggesting a role for HO-1 in osteoblast function in arthritis. This evidence concerns the gene TNFSF11 and arthritic joint disease.