Soluble glucocorticoid-induced tumor necrosis factor receptor (sGITR) stimulates osteoclast differentiation in response to receptor activator of NF-κB 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-κB 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)-β, and blockade of endogenous IFN-β 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-β.