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Involvement of ERK and p38 MAPK pathways on Interleukin‐33‐induced RANKL expression in osteoblastic cells

The receptor activator of NF‐κB ligand (RANKL)/osteoprotegerin (OPG) system is a well‐known key factor in osteoclast differentiation, and osteoblastic lineage cells are the major sources of RANKL and OPG in local bone tissue. Recently, a new molecule from the interleukin (IL)‐1 family, IL‐33, was identified. Here, we report the possible involvement of IL‐33 in RANKL and OPG expression, and the signaling pathways that are required for maximal IL‐33‐induced RANKL expression in MC3T3‐E1 osteoblastic cells. Stimulation with IL‐33 increased the mRNA expression and secretion of RANKL in MC3T3‐E1 cells. The IL‐33‐induced RANKL mRNA expression was inhibited by an anti‐IL‐33 monoclonal antibody. Furthermore, ERK and p38 MAPK inhibitors, but not a JNK inhibitor, suppressed IL‐33‐induced RANKL mRNA expression. On the other hand, IL‐33 had no effect on OPG mRNA expression and protein secretion. These results taken together suggest that IL‐33 stimulates RANKL expression through mechanisms dependent on the ERK and p38 MAPK pathways in MC3T3‐E1 cells.