Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis.

J Exp Med 2005 Sep;202(5):589-95

Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea.

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.

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http://dx.doi.org/10.1084/jem.20050978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212875PMC
September 2005
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References

(Supplied by CrossRef)

Nature. 2003

Endocr. Rev. 1999

J. Exp. Med. 2000

Cytokine Growth Factor Rev. 2003

Genes Cells. 1999

Genes Dev. 1999

Immunity. 2003

J. Exp. Med. 2000

J. Biol. Chem. 2000

Endocrinology. 2002

J. Clin. Invest. 2000

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