Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines

摘要: In unstimulated conditions osteoclast renewal occurs as a result of the stromal cell production key osteoclastogenic factors, receptor activator NFkB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Inflammation is known to cause increased osteoclastogenesis; however, mechanisms responsible for this phenomenon are poorly understood. We now show that interleukin-1 (IL-1) tumor necrosis alpha (TNFalpha), cytokines typically produced in inflammatory conditions, increase IL-7. This factor, turn, up-regulates by T cells leading stimulation (OC) formation. Although were found produce soluble forms both RANKL M-CSF, saturating concentrations osteoprotegerin failed inhibit approximately 40% OC formation, suggesting IL-7 acts via RANKL-dependent RANKL-independent pathways. Despite identification T-cell-secreted cytokine was not essential either or -independent secrete other capable substituting M-CSF action. On basis our data, we propose novel mechanism bone loss which induction from IL-1 TNFalpha leads cells. Thus, causes resorption involves activation T-cell-dependent augmentation osteoclastogenesis. (Blood. 2000;96:1873-1878)