Affordable Access

deepdyve-link
Publisher Website

Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

Authors
  • Khapli, Shruti M.
  • Tomar, Geetanjali B.
  • Barhanpurkar, Amruta P.
  • Gupta, Navita
  • Yogesha, S.D.
  • Pote, Satish T.
  • Wani, Mohan R.
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Publication Date
Jan 01, 2010
Volume
399
Issue
4
Pages
688–693
Identifiers
DOI: 10.1016/j.bbrc.2010.07.143
Source
Elsevier
Keywords
License
Unknown

Abstract

IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

Report this publication

Statistics

Seen <100 times