Activin A stimulates IkappaB-alpha/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors
| Autor: | T, Sugatani, U M, Alvarez, K A, Hruska |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cell Survival
Active Transport Cell Nucleus Osteoclasts Receptors Cytoplasmic and Nuclear Apoptosis Bone Marrow Cells Protein Serine-Threonine Kinases Receptors Tumor Necrosis Factor Mice NF-KappaB Inhibitor alpha Proto-Oncogene Proteins Animals Cells Cultured Glycoproteins Inhibin-beta Subunits Membrane Glycoproteins Receptor Activator of Nuclear Factor-kappa B Macrophage Colony-Stimulating Factor Macrophages TOR Serine-Threonine Kinases RANK Ligand NF-kappa B Osteoprotegerin Cell Differentiation Activins Mice Inbred C57BL I-kappa B Proteins bcl-Associated Death Protein Carrier Proteins Protein Kinases Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of cellular biochemistry. 90(1) |
| ISSN: | 0730-2312 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text