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.
Department of Oral Biology and Engineering, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8553, Japan.
Yuichi
Y
Mine
Seicho
S
Makihira
Yu
Y
Yamaguchi
Hideki
H
Tanaka
Hiroki
H
Nikawa
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D053245:RANK Ligand / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D053245:RANK Ligand; D048051:p38 Mitogen-Activated Protein Kinases
MAPK; RANKL; ST2L; bone remodeling; interleukin-33; osteoprotegerin