Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
Kim, Nacksung ; Kadono, Yuho ; Takami, Masamichi ; Lee, Junwon ; Lee, Seoung-Hoon ; Okada, Fumihiko ; Kim, Jung Ha ; Kobayashi, Takashi ; Odgren, Paul R. ; Nakano, Hiroyasu ... show 4 more
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Keywords
Carrier 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
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Abstract
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 site