Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells.
Osteoprotegerin (OPG) and osteoclast differentiation factor (ODF) are crucial regulators of osteoclastogenesis. To determine the biological role of interleukin (IL)-18 produced by stromal/osteoblastic cells in osteoclastogenesis, we examined the effects of IL-18 on the OPG and ODF mRNA levels in these cells. When bone marrow stromal ST2 cells, osteoblastic MC3T3-E1 cells, and mouse calvarial osteoblasts were stimulated with IL-18, the expression of OPG mRNA, but not ODF mRNA, was transiently increased, its expression reaching a maximal level at 3 h after the beginning of the culture. In accordance with this observation, all these cells expressed the mRNAs of two IL-18 receptor components and MyD88, an adapter molecule involved in IL-18 signaling. Moreover, in these cells, mitogen-activated protein kinase was phosphorylated after stimulation with IL-18. These results suggest that stromal/osteoblastic cells are IL-18-responsive cells and that IL-18 may inhibit osteoclastogenesis by up-regulating OPG expression, without stimulation of ODF production, in stromal/osteoblastic cells.
Makiishi-Shimobayashi
C
C
Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Tsujimura
T
T
Iwasaki
T
T
Yamada
N
N
Sugihara
A
A
Okamura
H
H
Hayashi
S
S
Terada
N
N
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D020382:Interleukin-18 / Q000494:pharmacology*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin / Q000235:genetics; D053724:Receptors, Interleukin-18; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D006023:Glycoproteins; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; D020928:Mitogen-Activated Protein Kinases