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Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis
Odgren Lab
  • Nacksung Kim, Chonnam National University Medical School
  • Yuho Kadono, University of Pennsylvania School of Medicine
  • Masamichi Takami, Showa University
  • Junwon Lee, Chonnam National University Medical School
  • Seoung-Hoon Lee, University of Pennsylvania School of Medicine
  • Fumihiko Okada, University of Pennsylvania School of Medicine
  • Jung Ha Kim, Chonnam National University Medical School
  • Takashi Kobayashi, University of Pennsylvania School of Medicine
  • Paul R. Odgren, University of Massachusetts Medical School
  • Hiroyasu Nakano, Juntendo University School of Medicine
  • Wen-Chen Yeh, University of Toronto
  • Sun-Kyeong Lee, University of Connecticut Health Center
  • Joseph A. Lorenzo, University of Connecticut Health Center
  • Yongwon Choi, University of Pennsylvania School of Medicine
UMMS Affiliation
Department of Cell Biology
Date
9-9-2005
Document Type
Article
Medical Subject Headings
Animals; 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
Disciplines
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.
Rights and Permissions
Citation: J Exp Med. 2005 Sep 5;202(5):589-95. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
16147974
Citation Information
Nacksung Kim, Yuho Kadono, Masamichi Takami, Junwon Lee, et al.. "Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis" Vol. 202 Iss. 5 (2005) ISSN: 0022-1007 (Linking)
Available at: http://works.bepress.com/paul_odgren/9/