| First Author | Kim N | Year | 2005 |
| Journal | J Exp Med | Volume | 202 |
| Issue | 5 | Pages | 589-95 |
| PubMed ID | 16147974 | Mgi Jnum | J:100699 |
| Mgi Id | MGI:3589318 | Doi | 10.1084/jem.20050978 |
| Citation | Kim N, et al. (2005) Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J Exp Med 202(5):589-95 |
| abstractText | Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE). Genetic deletion of TRANCE or its receptor, receptor activator of nuclear factor kappaB (RANK), results in severely osteopetrotic mice with no osteoclasts in their bones. TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis. Hence, the current paradigm holds that TRANCE-RANK interaction and subsequent signaling via TRAF6 are essential for the generation of functional osteoclasts. Surprisingly, we show that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-alpha in the presence of cofactors such as TGF-beta. We provide direct evidence against the current paradigm that the TRANCE-RANK-TRAF6 pathway is essential for osteoclast differentiation and suggest the potential existence of alternative routes for osteoclast differentiation. |
