| First Author | Miyamoto H | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 39 | Pages | 32479-84 |
| PubMed ID | 22865856 | Mgi Jnum | J:191592 |
| Mgi Id | MGI:5462143 | Doi | 10.1074/jbc.M112.358226 |
| Citation | Miyamoto H, et al. (2012) An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion. J Biol Chem 287(39):32479-84 |
| abstractText | Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs. |
