| First Author | Maruyama K | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 34 | Pages | 29114-24 |
| PubMed ID | 22773835 | Mgi Jnum | J:190237 |
| Mgi Id | MGI:5448478 | Doi | 10.1074/jbc.M112.347799 |
| Citation | Maruyama K, et al. (2012) TRAF family member-associated NF-kappaB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation. J Biol Chem 287(34):29114-24 |
| abstractText | The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-kappaB via TRAF6 activation. TRAF family member-associated NF-kappaB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank(-/-) mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank(-/-) cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-kappaB activation in response to RANKL stimulation. Tank(-/-) mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank(-/-) osteoblasts exhibited enhaced NF-kappaB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank(-/-) mice showed trabecular bone loss analogous to that in Tank(-/-) mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-kappaB, and is also important for proper bone remodeling. |
