Transcriptomics

Dataset Information

296

STAT5 is a key transcription factor IL-3-mediated inhibition of RANKL-induced osteoclastogenesis


ABSTRACT: Purpose: Among the diverse cytokines involved in osteoclast differentiation, IL-3 has been shown to inhibit RANKL-induced osteoclastogenesis. However, the mechanism underlying IL-3-mediated inhibition of osteoclast differentiation is not fully understood. In the present study, we demonstrate that IL-3 activation of STAT5 inhibits RANKL-induced osteoclastogenesis through the induction of Id genes. Methods: To investigate the effect of STAT5 on osteoclast differentiation and IL-3-mediated inhibition of osteoclast differentiation, bone marrow derived macrophages isolated from STAT5 wild-type (Stat5fl/fl) or STAT5 cKO (STAT5;MX1-Cre) were differentiated to osteoclast in the presence of M-CSF and RANKL with or without IL-3; and bone marrow derived macrophges from STAT5 wild-type and STAT5 cKO were overexpressed with PMX-FIG (control) or STAT5A1*6 (constitutively active form of STAT5A) and differentiated to osteoclast. To analyze bone phenotype, femurs and tibiae of 16 week-old STAT5 wild-type and STAT5 cKO were subjected to micro CT analysis and histomorphometry, respectively. Results: Overexpression of STAT5 inhibited RANKL-induced osteoclastogenesis. However, RANKL did not regulate either expression or activation of STAT5 during osteoclast differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of osteoclastogenesis, suggesting that STAT5 plays an important role in IL-3-mediated inhibition of osteoclast differentiation. In addition, IL-3-induced STAT5 activation upregulated expression of the Id1 and Id2 genes, which are negative regulators of osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells reversed osteoclast development recovered from IL-3-mediated inhibition. Moreover, micro-computed tomography and histomorphometric analysis revealed that STAT5 conditional knockout mice showed reduced bone mass, with an increased number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast differentiation less effectively in STAT5 conditional knockout mice than in wild-type mice in a RANKL injection model. Conclusion: Taken together, our results suggest that STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis through Id gene expression. Examination of 4 different combination of osteoclast differentiation condition of bone marrow derived macrophages.

ORGANISM(S): Mus musculus  

SUBMITTER: Jongwon Lee   Nacksung Kim  Semun Seong 

PROVIDER: E-GEOD-76988 | ArrayExpress | 2016-08-03

SECONDARY ACCESSION(S): SRP068592GSE76988PRJNA309183

REPOSITORIES: GEO, ArrayExpress, ENA

Similar Datasets

2014-11-01 | E-GEOD-41992 | ArrayExpress
2010-03-22 | GSE20850 | GEO
2015-12-31 | E-GEOD-53017 | ArrayExpress
2014-06-02 | E-GEOD-58146 | ArrayExpress
2010-03-22 | E-GEOD-20850 | ArrayExpress
2011-09-30 | E-GEOD-29106 | ArrayExpress
2018-01-24 | PXD006448 | Pride
2014-11-05 | E-GEOD-54139 | ArrayExpress
| PRJNA309183 | ENA
2011-09-30 | E-GEOD-29107 | ArrayExpress