Conditional deletion of CD98hc inhibits osteoclast development

Hideki Tsumura, Morihiro Ito, Masamichi Takami, Miyuki Arai, Xiao Kang Li, Toshio Hamatani, Arisa Igarashi, Shuji Takada, Kenji Miyado, Akihiro Umezawa, Yasuhiko Ito

Research output: Contribution to journalArticle

Abstract

The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)2 vitamin D3, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hc-defect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport.

Original languageEnglish
Pages (from-to)203-210
Number of pages8
JournalBiochemistry and Biophysics Reports
Volume5
DOIs
Publication statusPublished - 2016 Mar 1

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Keywords

  • Amino acid starvation
  • Amino acid transport
  • CD98 heavy chain
  • Integrin signaling
  • Osteoclast formation
  • RANKL

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Tsumura, H., Ito, M., Takami, M., Arai, M., Li, X. K., Hamatani, T., Igarashi, A., Takada, S., Miyado, K., Umezawa, A., & Ito, Y. (2016). Conditional deletion of CD98hc inhibits osteoclast development. Biochemistry and Biophysics Reports, 5, 203-210. https://doi.org/10.1016/j.bbrep.2015.11.023