| First Author | Khapli SM | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 399 |
| Issue | 4 | Pages | 688-93 |
| PubMed ID | 20691668 | Mgi Jnum | J:164898 |
| Mgi Id | MGI:4835604 | Doi | 10.1016/j.bbrc.2010.07.143 |
| Citation | Khapli SM, et al. (2010) Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis. Biochem Biophys Res Commun 399(4):688-93 |
| abstractText | 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-kappaB (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. |
