PMID- 12938156
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20220311
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 90
IP  - 1
DP  - 2003 Sep 1
TI  - Activin A stimulates IkappaB-alpha/NFkappaB and RANK expression for osteoclast 
      differentiation, but not AKT survival pathway in osteoclast precursors.
PG  - 59-67
AB  - 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 mechanisms by which activin A functions during 
      osteoclastogenesis are not 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 (mTOR) for survival in osteoclast precursors in vitro. Activin A alone 
      failed to activate Akt, BAD, and mTOR 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.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Sugatani, T
AU  - Sugatani T
AD  - Department of Pediatrics, Washington University School of Medicine, St. Louis, 
      Missouri 63110, USA. sugatani_t@kids.wustl.edu
FAU - Alvarez, U M
AU  - Alvarez UM
FAU - Hruska, K A
AU  - Hruska KA
LA  - eng
GR  - AR41677/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Bad protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Osteoprotegerin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tnfrsf11a protein, mouse)
RN  - 0 (Tnfrsf11b protein, mouse)
RN  - 0 (Tnfsf11 protein, mouse)
RN  - 0 (activin A)
RN  - 0 (bcl-Associated Death Protein)
RN  - 104625-48-1 (Activins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 93443-12-0 (Inhibin-beta Subunits)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Activins/*metabolism
MH  - Animals
MH  - Apoptosis/physiology
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Carrier Proteins/metabolism
MH  - Cell Differentiation/*physiology
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Glycoproteins/*metabolism
MH  - I-kappa B Proteins/*metabolism
MH  - Inhibin-beta Subunits/*metabolism
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Macrophages/cytology/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Osteoclasts/*physiology
MH  - Osteoprotegerin
MH  - Protein Kinases/metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - RANK Ligand
MH  - Receptor Activator of Nuclear Factor-kappa B
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Receptors, Tumor Necrosis Factor
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
MH  - bcl-Associated Death Protein
EDAT- 2003/08/26 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/08/26 05:00
PHST- 2003/08/26 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/08/26 05:00 [entrez]
AID - 10.1002/jcb.10613 [doi]
PST - ppublish
SO  - J Cell Biochem. 2003 Sep 1;90(1):59-67. doi: 10.1002/jcb.10613.