Previous studies have shown that deletion of RL-D5 or RL-D6 partly inhibits OSM-induced RANKL expression in osteoblastic cells, but the importance of RL-D4 in physiological or pathological bone metabolism has not been explored.32–35 Therefore, we evaluated the role of the RL-D4 region in periodontitis-induced bone loss by generating mice lacking the RL-D4 region using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing technology. The gene discussed is TNFSF11; the disease is periodontitis.