Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
Authors
Kim, NacksungKadono, Yuho
Takami, Masamichi
Lee, Junwon
Lee, Seoung-Hoon
Okada, Fumihiko
Kim, Jung Ha
Kobayashi, Takashi
Odgren, Paul R.
Nakano, Hiroyasu
Yeh, Wen-Chen
Lee, Sun-Kyeong
Lorenzo, Joseph A.
Choi, Yongwon
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2005-09-09Keywords
AnimalsCarrier Proteins
Cell Differentiation
DNA Primers
Gene Deletion
Hematopoietic Stem Cells
Histological Techniques
Lymphotoxin-alpha
Male
Membrane Glycoproteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoclasts
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
TNF Receptor-Associated Factor 6
Tumor Necrosis Factor-alpha
Cell Biology
Metadata
Show full item recordAbstract
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.Source
J Exp Med. 2005 Sep 5;202(5):589-95. Link to article on publisher's siteDOI
10.1084/jem.20050978Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42870PubMed ID
16147974Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1084/jem.20050978