Yoshiaki Azuma

TRAF5 functions in both RANKL- and TNFα-induced osteoclastogenesis

Although TRAF6 is essential for both RANKL‐ and TNFα‐induced osteoclastogenesis, it has remained unclear whether other members of the TRAF family are involved in osteoclastogenesis. We examined TRAF5 function in both RANKL‐ and TNFα‐induced osteoclastogenesis by using osteoclast progenitor cells from TRAF5‐deficient mice. The results demonstrated that RANKL or TNFα 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 NF‐κB activation was apparently observed in osteoclast progenitor cells. In the parathyroid hormone (PTH)‐induced hypercalcemia model, calcium concentration peaked at day 3 after administration. However, in TRAF5‐deficient mice, this peak was delayed and found at day 5, showing less effective osteoclast differentiation. Thus, we have provided the first evidence showing that TRAF5 is involved in osteoclastogenesis.

Tumor Necrosis Factor α‐Induced Osteoclastogenesis Requires Tumor Necrosis Factor Receptor‐Associated Factor 6

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.