An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion

Hiroya Miyamoto, Eri Katsuyama, Yoshiteru Miyauchi, Hiroko Hoshi, Kana Miyamoto, Yuiko Sato, Tami Kobayashi, Ryotaro Iwasaki, Shigeyuki Yoshida, Tomoaki Mori, Hiroya Kanagawa, Atsuhiro Fujie, Wu Hao, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama, Takeshi Miyamoto

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)32479-32484
Number of pages6
JournalJournal of Biological Chemistry
Volume287
Issue number39
DOIs
Publication statusPublished - 2012 Sep 21

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Miyamoto, H., Katsuyama, E., Miyauchi, Y., Hoshi, H., Miyamoto, K., Sato, Y., Kobayashi, T., Iwasaki, R., Yoshida, S., Mori, T., Kanagawa, H., Fujie, A., Hao, W., Morioka, H., Matsumoto, M., Toyama, Y., & Miyamoto, T. (2012). An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion. Journal of Biological Chemistry, 287(39), 32479-32484. https://doi.org/10.1074/jbc.M112.358226