Activin A stimulates IκB-α/NFκB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors

Toshifumi Sugatani, U. M. Alvarez, K. A. Hruska

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalJournal of cellular biochemistry
Volume90
Issue number1
DOIs
StatePublished - Sep 1 2003

Keywords

  • AKT
  • Activin A
  • MTOR
  • NFκB
  • Osteoclast differentiation
  • RANK
  • Survival

Fingerprint

Dive into the research topics of 'Activin A stimulates IκB-α/NFκB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors'. Together they form a unique fingerprint.

Cite this