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NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP).
- Kabsun Kim, Seoung-Hoon Lee, Jung Ha Kim, Yongwon Choi, Nacksung Kim
- BiologyMolecular endocrinology
The data indicate for the first time that the NFATc1/Atp6v0d2 and DC-STAMP signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption.
v-ATPase V0 subunit d2–deficient mice exhibit impaired osteoclast fusion and increased bone formation
It is shown that inactivation of Atp6v0d2 in mice results in markedly increased bone mass due to defective osteoclasts and enhanced bone formation, and genetic data is provided showing that it is possible to simultaneously inhibit osteoclast maturation and stimulate bone formation by therapeutically targeting the function of a single gene.
Osteoclast differentiation independent of the TRANCE–RANK–TRAF6 axis
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.
Nuclear Factor of Activated T Cells c1 Induces Osteoclast-associated Receptor Gene Expression during Tumor Necrosis Factor-related Activation-induced Cytokine-mediated Osteoclastogenesis*
NFATc1 is an important transcription factor in the induction of OSCAR during osteoclastogenesis and its activation implies the presence of a positive feedback circuit of TRANCE-induced activation of NFAT c1, necessary for efficient differentiation of osteoclasts.
The Tec Family Tyrosine Kinase Btk Regulates RANKL-induced Osteoclast Maturation*
- Seoung-Hoon Lee, Taesoo Kim, Daewon Jeong, Nacksung Kim, Yongwon Choi
- BiologyJournal of Biological Chemistry
- 25 April 2008
Evidence is provided that Btk plays a critical role in osteoclast multinucleation by modulating the activity of NFATc1 and this deficiency in the Xid mutant osteoclasts was completely rescued by the introduction of a constitutively active form of NFatc1 into bone marrow-derived macrophages.
Interleukin-33 stimulates formation of functional osteoclasts from human CD14+ monocytes
This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes.
Sirtuin 3 (SIRT3) maintains bone homeostasis by regulating AMPK-PGC-1β axis in mice
It is shown that Sirt3 is a key regulatory molecule to maintain bone homeostasis and an auto-regulatory feedback mechanism operates to induce its own inhibitor SIRT3 by PGC-1β.
Tmem64 modulates calcium signaling during RANKL-mediated osteoclast differentiation.
Id helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation.
Results reveal both a new facet of negative regulation, mediated by Id proteins, as well as the mechanism whereby TRANCE signaling overcomes it, allowing osteoclastogenesis to proceed.
Osteoimmunology: cytokines and the skeletal system.
A more complete appreciation of the interactions between immune and bone cells should lead to better therapeutic strategies for diseases that affect either or both systems.