Bartell et al. (2014), experimentally proved the role of TNFSF11 in the downregulation of the Forkhead box proteins. In accordance with this, our analysis showed an upregulation of TNFSF11 in the ODP network. Finally, our analysis reported the upregulation of the cytokine receptor colony stimulating factor 1 receptor (CSF1R) which is also required for osteoclastogenesis via PI3K-AKT pathway. The proposed model consisting of all the signaling routes promoting osteoclastogenesis via generation of ROS in the RA synovium is summarized in Fig. 10. This evidence concerns the gene PIK3CD and rheumatoid arthritis.