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Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
IL-1 mediates TNF-induced osteoclastogenesis.
Shi Wei1, Hideki Kitaura, Ping Zhou
1Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of Clinical Investigation
|January 26, 2005
Summary
Interleukin-1 (IL-1) mediates tumor necrosis factor (TNF)-induced osteoclast formation by enhancing receptor activator NF-kappaB ligand (RANKL) expression and directly stimulating osteoclast precursors.
Area of Science:
- Immunology
- Bone Biology
- Rheumatology
Background:
- Tumor necrosis factor (TNF)-induced receptor activator NF-kappaB ligand (RANKL) synthesis by bone marrow stromal cells is crucial for inflammatory osteolysis.
- Interleukin-1 receptor antagonist (IL-1Ra) or IL-1 receptor type I (IL-1RI)-deficient stromal cells abolish TNF-induced RANKL synthesis.
Purpose of the Study:
- To investigate the role of IL-1 in TNF-induced osteoclastogenesis and periarticular osteolysis.
- To elucidate the mechanisms by which IL-1 mediates TNF's osteoclastogenic effects.
Main Methods:
- Utilized IL-1 receptor antagonist (IL-1Ra) and IL-1RI-deficient mice models.
- Assessed TNF-stimulated osteoclastogenesis in vitro (marrow macrophage and stromal cell co-cultures) and in vivo.
- Examined IL-1's direct effects on osteoclast precursors and RANKL expression.
Main Results:
- TNF induces stromal cell expression of IL-1 and IL-1RI, suggesting sequential signaling.
- TNF-stimulated osteoclastogenesis was reduced by approximately 50% with IL-1Ra or IL-1RI-deficient stromal cells in vitro and in vivo.
- IL-1 directly promoted osteoclast precursor differentiation and enhanced RANKL expression by stromal cells, mediated by p38 MAPK.
Conclusions:
- IL-1 plays a critical role in TNF-induced periarticular osteolysis by regulating RANKL expression and directly affecting osteoclast precursors.
- IL-1 mediates the osteoclastogenic effects of TNF through enhanced RANKL production and direct stimulation of osteoclast differentiation.
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