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Activin A stimulates IκB‐α/NFκB and rank expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors
Author(s) -
Sugatani T.,
Alvarez U.M.,
Hruska K.A.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10613
Subject(s) - rankl , osteoclast , protein kinase b , pi3k/akt/mtor pathway , signal transduction , rank ligand , microbiology and biotechnology , nf κb , activator (genetics) , medicine , endocrinology , biology , chemistry , cancer research , receptor
Recent studies have reported that activin A enhances osteoclastogenesis in cultures of mouse bone marrow cells stimulated with receptor activator of nuclear factor‐κB 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‐κB (NFκB) nuclear translocation and activates the Akt/PKB cell survival pathway. Here we report that activin A alone activates IκB‐α, and stimulates nuclear translocation of NFκB and receptor activator of nuclear factor‐κB (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 IκB‐α and induced nuclear translocation of phosphorylated‐NFκB, and it also enhanced RANK expression in osteoclast precursors. Moreover, activin A enhanced RANKL‐ and M‐CSF‐stimulated nuclear translocation of NFκB. 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 NFκB pathway, but not survival in osteoclast precursors in vitro, but it is, thus, insufficient as a sole stimulus to osteoclastogenesis. J. Cell. Biochem. 90: 59–67, 2003. © 2003 Wiley‐Liss, Inc.