Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) stimulates osteoclast differentiation in response to receptor activator of NF-kappaB ligand (RANKL) in osteoclast cells.
We found that treatment of osteoclast (OC) precursors with soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) promoted osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF) and receptor for activation of nuclear factor-kappaB ligand (RANKL). Low levels of GITR and its ligand were expressed on the surface of OC precursor cells after incubation with RANKL. Stimulation of osteoclastogenesis by sGITR was blocked by neutralization with anti-GITR ligand antibody (Ab), whereas endogenous GITR did not affect osteoclastogenesis, indicating that enhancement of osteoclastogenesis by sGITR involves signaling via GITR ligand. The addition of sGITR decreased the level of interferon (IFN)-beta, and blockade of endogenous IFN-beta did not affect osteoclastogenesis stimulated by sGITR. We conclude that sGITR enhances osteoclastogenesis by acting on OC precursor cells to lower the level of IFN-beta.
Shin
Hyun-Hee
HH
Department of Biological Sciences and the Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea.
Kim
Soo-Jin
SJ
Lee
Dong-Sul
DS
Choi
Hye-Seon
HS
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein; D016899:Interferon-beta / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C106544:Tnfrsf18 protein, mouse; C505689:Tnfsf11 protein, mouse; D016899:Interferon-beta