title: IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression.
abstract: Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression.
authors: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan; Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Hiroyasu
authors: H
authors: Kiyomiya
authors: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Wataru
authors: W
authors: Ariyoshi
authors: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Toshinori
authors: T
authors: Okinaga
authors: Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Takeshi
authors: T
authors: Kaneuji
authors: Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Sho
authors: S
authors: Mitsugi
authors: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan; Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Takuma
authors: T
authors: Sakurai
authors: Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Manabu
authors: M
authors: Habu
authors: Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Izumi
authors: I
authors: Yoshioka
authors: Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan.
authors: Kazuhiro
authors: K
authors: Tominaga
authors: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan. Electronic address: tatsujin@kyu-dent.ac.jp.
authors: Tatsuji
authors: T
authors: Nishihara
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000502:physiology*; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099185:Interferon Regulatory Factor-8
chemical_list: D017931:DNA Primers; D050835:Interferon Regulatory Factors; D000067596:Interleukin-33; D007378:Interleukins; D050778:NFATC Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053245:RANK Ligand; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C506535:Il33 protein, mouse; C494005:Nfatc1 protein, mouse; C513258:Prdm1 protein, mouse; C505689:Tnfsf11 protein, mouse
keywords: Blimp-1; IL-33; IRF-8; Osteoclastogenesis