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Conditional deletion of CD98hc inhibits osteoclast development

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 CD98hc(flox/flox)LysM-cre peritoneal macrophages (CD98hc-defect macrophages). Perito...

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Detalles Bibliográficos
Autores principales: Tsumura, Hideki, Ito, Morihiro, Takami, Masamichi, Arai, Miyuki, Li, Xiao-Kang, Hamatani, Toshio, Igarashi, Arisa, Takada, Shuji, Miyado, Kenji, Umezawa, Akihiro, Ito, Yasuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600448/
https://www.ncbi.nlm.nih.gov/pubmed/28955825
http://dx.doi.org/10.1016/j.bbrep.2015.11.023
Descripción
Sumario: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 CD98hc(flox/flox)LysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)(2) vitamin D(3), 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.