Journal
JOURNAL OF CELL BIOLOGY
Volume 148, Issue 2, Pages 333-342Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.148.2.333
Keywords
osteoclast; adenovirus; apoptosis; Ras; NF-kappa B
Categories
Ask authors/readers for more resources
To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-kappa B) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (Ras(DN)), constitutively active MEK1 (MEKCA), dominant negative I kappa B kinase 2 (IKKDN), and constitutively active IKK2 (IKKCA). Inhibiting ERK activity by Ras(DN) over-expression rapidly induced the apoptosis of osteoclastlike cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEKCA remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs, Inhibition of NF-kappa B pathway with IKKDN virus suppressed the pit-forming activity of OCLs and NF-kappa B activation by IKKCA expression upregulated it without affecting their survival. Interleukin 1 alpha (IL-1 alpha) strongly induced ERK activation as well as NF-kappa B activation. Ras(DN) virus partially inhibited ERK activation, and OCL survival promoted by IL-1 alpha. Inhibiting NF-kappa B activation by IKKDN virus significantly suppressed the pit-forming activity enhanced by IL-1 alpha, These results indicate that ERK and NF-kappa B regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-kappa B regulates osteoclast activation for bone resorption.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available