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 CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritone...
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Elsevier
2016-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580815001430 |
| _version_ | 1818439005940744192 |
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| author | Hideki Tsumura Morihiro Ito Masamichi Takami Miyuki Arai Xiao-Kang Li Toshio Hamatani Arisa Igarashi Shuji Takada Kenji Miyado Akihiro Umezawa Yasuhiko Ito |
| author_facet | Hideki Tsumura Morihiro Ito Masamichi Takami Miyuki Arai Xiao-Kang Li Toshio Hamatani Arisa Igarashi Shuji Takada Kenji Miyado Akihiro Umezawa Yasuhiko Ito |
| author_sort | Hideki Tsumura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T17:49:35Z |
| format | Article |
| id | doaj.art-d92eb2288158495182df56bfd8e661da |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-14T17:49:35Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-d92eb2288158495182df56bfd8e661da2022-12-21T22:52:40ZengElsevierBiochemistry and Biophysics Reports2405-58082016-03-015C20321010.1016/j.bbrep.2015.11.023Conditional deletion of CD98hc inhibits osteoclast developmentHideki Tsumura0Morihiro Ito1Masamichi Takami2Miyuki Arai3Xiao-Kang Li4Toshio Hamatani5Arisa Igarashi6Shuji Takada7Kenji Miyado8Akihiro Umezawa9Yasuhiko Ito10Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, JapanDepartment of Microbiology, College of Life and Health Science, Chubu University, 1200 Matumoto-Chou, Kasugai-City, Aichi-Prefecture 487-8501, JapanDepartment of Pharmacology, School of Dentistry, Showa University, Tokyo, JapanDivision of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, JapanDivision for Radiation Safety and Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, JapanDepartment of Obstetrics and Gynaecology, Keio University School of Medicine, Tokyo, JapanDepartment of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, JapanDepartment of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, JapanDepartment of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, JapanDepartment of Reproductive Biology, National Research Institute for Child Health and Development, Tokyo, JapanDepartment of Microbiology, College of Life and Health Science, Chubu University, 1200 Matumoto-Chou, Kasugai-City, Aichi-Prefecture 487-8501, JapanThe 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.http://www.sciencedirect.com/science/article/pii/S2405580815001430CD98 heavy chainOsteoclast formationRANKLIntegrin signalingAmino acid transportAmino acid starvation |
| spellingShingle | Hideki Tsumura Morihiro Ito Masamichi Takami Miyuki Arai Xiao-Kang Li Toshio Hamatani Arisa Igarashi Shuji Takada Kenji Miyado Akihiro Umezawa Yasuhiko Ito Conditional deletion of CD98hc inhibits osteoclast development Biochemistry and Biophysics Reports CD98 heavy chain Osteoclast formation RANKL Integrin signaling Amino acid transport Amino acid starvation |
| title | Conditional deletion of CD98hc inhibits osteoclast development |
| title_full | Conditional deletion of CD98hc inhibits osteoclast development |
| title_fullStr | Conditional deletion of CD98hc inhibits osteoclast development |
| title_full_unstemmed | Conditional deletion of CD98hc inhibits osteoclast development |
| title_short | Conditional deletion of CD98hc inhibits osteoclast development |
| title_sort | conditional deletion of cd98hc inhibits osteoclast development |
| topic | CD98 heavy chain Osteoclast formation RANKL Integrin signaling Amino acid transport Amino acid starvation |
| url | http://www.sciencedirect.com/science/article/pii/S2405580815001430 |
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