Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 90, Issue 1, Pages 59-67Publisher
WILEY
DOI: 10.1002/jcb.10613
Keywords
activin A; NF kappa B; RANK; osteoclast differentiation; survival; AKT; mTOR
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Funding
- NIAMS NIH HHS [AR41677] Funding Source: Medline
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Recent studies have reported that activin A enhances osteoclastogenesis in cultures of mouse bone marrow cells stimulated with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). However, the exact rnechanisms by which activin A functions during osteoclastogenesis are riot clear. RANKL stimulation of RANK/TRAF6 signaling increases nuclear factor-kappaB (NFkappaB) nuclear translocation and activates the Akt/PKB cell survival pathway. Here we report that activin A alone activates IkappaB-alpha, and stimulates nuclear translocation of NFkappaB and receptor activator of nuclear factor-kappaB (RANK) expression for osteoclastogenesis, but not Akt/PKB Survival signal transduction including BAD and mammalian target of rapamycin (rnTOR) for survival in osteoclast precursors in vitro. Activin A alone failed to activate Akt, BAD, and rnTOR by immunoblotting, and it also failed to prevent apoptosis in osteoclast precursors. While activin A activated IkappaB-alpha and induced nuclear translocation of phosphorylated-NFkappaB, and it also enhanced RANK expression in osteoclast precursors. Moreover, activin A enhanced RANKL- and M-CSF-stimulated nuclear translocation of NFkappaB. Our data suggest that activin A enhances osteoclastogenesis treated with RANKL and M-CSF via stimulation of RANK, thereby increasing the RANKL stimulation. Activin A alone activated the NFkappaB pathway, but not survival in osteoclast precursors in vitro, but it is, thus, insufficient as a sole stimulus to osteoclastogenesis.
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