Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis.
Nacksung Kim,Yuho Kadono,Masamichi Takami,Junwon Lee,Seoung Hoon Lee,Fumihiko Okada,Jung Ha Kim,Takashi Kobayashi,Paul R. Odgren,Hiroyasu Nakano,Wen-Chen Yeh,Sun-Kyeong Lee,Joseph A. Lorenzo,Yongwon Choi +13 more
Reads0
Chats0
TLDR
Surprisingly, it is shown that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-α in the presence of cofactors such as TGF-β.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 factorB (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- � in the presence of cofactors such as TGF- � . 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.read more
Citations
More filters
Journal ArticleDOI
Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems
TL;DR: The two systems should be understood to be integrated and operating in the context of the 'osteoimmune' system, a heuristic concept that provides not only a framework for obtaining new insights by basic research, but also a scientific basis for the discovery of novel treatments for diseases related to both systems.
Journal ArticleDOI
Functions of RANKL/RANK/OPG in bone modeling and remodeling.
Brendan F. Boyce,Lianping Xing +1 more
TL;DR: The current understanding of the role of the RANKL/RANK/OPG system in bone modeling and remodeling is reviewed to show that the relative concentration of RankL and OPG in bone is a major determinant of bone mass and strength.
Journal ArticleDOI
The molecular understanding of osteoclast differentiation.
TL;DR: The RANKL signaling pathway has promise as a strategy for suppressing the excessive osteoclast formation characteristic of a variety of bone diseases and is controlled by an epigenetic mechanism, which has profound implications for the general mechanism of irreversible cell fate determination.
Journal ArticleDOI
Estrogen deficiency and bone loss: an inflammatory tale
TL;DR: The current understanding of the process of estrogen deficiency-mediated bone destruction is presented and some recent findings and hypotheses to explain estrogen action in bone are explored.
Journal ArticleDOI
Osteoclasts: what do they do and how do they do it?
TL;DR: A number of key observations provide insights into the mechanisms by which precursors commit to the osteoclast phenotype and how the mature cell degrades bone.
References
More filters
Journal ArticleDOI
Osteoclast differentiation and activation
TL;DR: Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoporosis and activation of bone resorption, and how hormonal signals impact bone structure and mass.
Journal ArticleDOI
Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families.
TL;DR: Osteoblasts/stromal cells can now be replaced with RANKL and M-CSF in dealing with the whole life of osteoclasts, and new ways to treat several metabolic bone diseases caused by abnormal osteoclast recruitment and functions will be established.
Journal ArticleDOI
Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts.
Hiroshi Takayanagi,Sunhwa Kim,Takako Koga,Takako Koga,Hiroshi Nishina,Masashi Isshiki,Hiroki Yoshida,Hiroki Yoshida,Akio Saiura,Miho Isobe,Miho Isobe,Taeko Yokochi,Jun-ichiro Inoue,Erwin F. Wagner,Tak W. Mak,Tatsuhiko Kodama,Tadatsugu Taniguchi +16 more
TL;DR: RANKL selectively induces NFATc1 expression via TRAF6 and c-Fos signaling pathways, and may represent a master switch for regulating terminal differentiation of osteoclasts, functioning downstream of RANKL.
Journal ArticleDOI
RANK is essential for osteoclast and lymph node development.
William C. Dougall,Moira Glaccum,Keith Charrier,Kathy Rohrbach,Kenneth Brasel,T De Smedt,E Daro,Jeffrey S. Smith,Mark E. Tometsko,C. R. Maliszewski,Allison P. Armstrong,V Shen,S Bain,David Cosman,Dirk M. Anderson,Philip J. Morrissey,Jacques J. Peschon,JoAnn C. L. Schuh +17 more
TL;DR: Investigating the physiological role of the TNF receptor (TNFR) family member, RANK, revealed that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.
Journal ArticleDOI
TRAF6 is a signal transducer for interleukin-1
TL;DR: The identification of a new TRAF family member is reported, designated TRAF6, which indicates that TRAF proteins may function as signal transducers for distinct receptor families and that TRAf6 participates in IL-1 signalling.
Related Papers (5)
Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation
David L. Lacey,Emma Timms,Hong-Lin Tan,Michael J. Kelley,Colin R. Dunstan,Tim Burgess,Robin Elliott,Anne Colombero,Gary Elliott,S. Scully,Hailing Hsu,John K. Sullivan,Nessa Hawkins,E. Davy,C. Capparelli,Alana Eli,Yi-xin Qian,Steve Kaufman,Ildiko Sarosi,Victoria Shalhoub,Giorgio Senaldi,Jane Guo,John M. Delaney,William J. Boyle +23 more