Tumor necrosis factor α-induced osteoclastogenesis requires tumor necrosis factor receptor-associated factor 6

Abstract

Although tumor necrosis factor receptor-associated factor 6 (TRAF6) is required in receptor activator of NF-κB-receptor activator of NF-κB ligand (RANK-RANKL) signaling for osteoclastogenesis, it has remained unclear whether TRAF6 is crucial in tumor necrosis factor α (TNF-α)-induced osteoclastogenesis. We examined TRAF6 function in the TNF-α-induced osteoclastogenesis by using osteoclast progenitor cells from TRAF6-deficient mice. The results indicated that TNF-α did not effectively induce osteoclast differentiation from osteoclast progenitor cells derived from these mice into mature multinucleated osteoclasts, although c-jun N-terminal kinase (JNK) and TNF-α activation was observed in osteoclast progenitor cells. Thus, we have provided the first evidence showing that TRAF6 is involved in TNF-α-induced osteoclastogenesis.