| First Author | Hirose J | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 1 | Pages | 153-63 |
| PubMed ID | 24367002 | Mgi Jnum | J:208357 |
| Mgi Id | MGI:5562970 | Doi | 10.1084/jem.20130538 |
| Citation | Hirose J, et al. (2014) Bone resorption is regulated by cell-autonomous negative feedback loop of Stat5-Dusp axis in the osteoclast. J Exp Med 211(1):153-63 |
| abstractText | Signal transducer and activator of transcription 5 (Stat5) is essential for cytokine-regulated processes such as proliferation, differentiation, and survival in hematopoietic cells. To investigate the role of Stat5 in osteoclasts, we generated mice with an osteoclast-specific conditional deletion of Stat5 (Stat5 conditional knockout [cKO] mice) and analyzed their bone phenotype. Stat5 cKO mice exhibited osteoporosis caused by an increased bone-resorbing activity of osteoclasts. The activity of mitogen-activated protein kinases (MAPKs), in particular extracellular signal-related kinase, was increased in Stat5 cKO osteoclasts, whereas the expression of the MAPK phosphatases dual specificity phosphatase 1 (Dusp1) and Dusp2 was significantly decreased. Interleukin-3 (IL-3) stimulated the phosphorylation and nuclear translocation of Stat5 in osteoclasts, and Stat5 expression was up-regulated in response to receptor activator of nuclear factor kappaB ligand (RANKL). The results suggest that Stat5 negatively regulates the bone-resorbing function of osteoclasts by promoting Dusp1 and Dusp2 expression, and IL-3 promotes Stat5 activation in osteoclasts. |
