IL-1 mediates TNF-induced osteoclastogenesis

TNF-induced receptor activator NF-kappaB ligand (RANKL) synthesis by bone marrow stromal cells is a fundamental component of inflammatory osteolysis. We found that this process was abolished by IL-1 receptor antagonist (IL-1Ra) or in stromal cells derived from type I IL-1 receptor-deficient (IL-1RI-deficient) mice. Reflecting sequential signaling of the cytokines TNF and IL-1, TNF induces stromal cell expression of IL-1 and IL-1RI. These data suggest that TNF regulates RANKL expression via IL-1, and, therefore, IL-1 plays a role in TNF-induced periarticular osteolysis. Consistent with this posture, TNF-stimulated osteoclastogenesis in cultures consisting of WT marrow macrophages and stromal cells exposed to…

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  National Institutes of Health

  Award: DK56341