Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells

Biochem Biophys Res Commun. 2001 Feb 23;281(2):361-6. doi: 10.1006/bbrc.2001.4380.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Animals, Newborn
  • Antigens, Differentiation / genetics
  • Blotting, Western
  • Cell Line
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glycoproteins / genetics*
  • Interleukin-18 / pharmacology*
  • Interleukin-18 Receptor alpha Subunit
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Myeloid Differentiation Factor 88
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoprotegerin
  • Phosphorylation / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Immunologic*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-18
  • Receptors, Tumor Necrosis Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / cytology
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Up-Regulation / drug effects


  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Glycoproteins
  • Il18r1 protein, mouse
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Osteoprotegerin
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Immunologic
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf11b protein, mouse
  • Mitogen-Activated Protein Kinases