Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts
Abstract Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecul...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2019-01-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-018-0201-3 |
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| author | Sung-Jin Bae Min Wook Shin Taekwon Son Hye Shin Lee Ji Soo Chae Sejin Jeon Goo Taeg Oh Kyu-Won Kim |
| author_facet | Sung-Jin Bae Min Wook Shin Taekwon Son Hye Shin Lee Ji Soo Chae Sejin Jeon Goo Taeg Oh Kyu-Won Kim |
| author_sort | Sung-Jin Bae |
| collection | DOAJ |
| description | Abstract Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1−/− mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs. |
| format | Article |
| id | doaj-art-3a8e8a44cfb0448eba63e4077fc6c255 |
| institution | OA Journals |
| issn | 1226-3613 2092-6413 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-3a8e8a44cfb0448eba63e4077fc6c2552025-08-20T02:05:46ZengNature Publishing GroupExperimental and Molecular Medicine1226-36132092-64132019-01-0151111610.1038/s12276-018-0201-3Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclastsSung-Jin Bae0Min Wook Shin1Taekwon Son2Hye Shin Lee3Ji Soo Chae4Sejin Jeon5Goo Taeg Oh6Kyu-Won Kim7College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Life Sciences and Technology, PerkinElmerDepartment of Life Sciences, Ewha Womans UniversityDepartment of Life Sciences, Ewha Womans UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityAbstract Osteoclasts (OCs) are bone-resorbing cells that originate from hematopoietic stem cells and develop through the fusion of mononuclear myeloid precursors. Dysregulation of OC development causes bone disorders such as osteopetrosis, osteoporosis, and rheumatoid arthritis. Although the molecular mechanisms underlying osteoclastogenesis have been well established, the means by which OCs maintain their survival during OC development remain unknown. We found that Ninjurin1 (Ninj1) expression is dynamically regulated during osteoclastogenesis and that Ninj1−/− mice exhibit increased trabecular bone volume owing to impaired OC development. Ninj1 deficiency did not alter OC differentiation, transmigration, fusion, or actin ring formation but increased Caspase-9-dependent intrinsic apoptosis in prefusion OCs (preOCs). Overexpression of Ninj1 enhanced the survival of mouse macrophage/preOC RAW264.7 cells in osteoclastogenic culture, suggesting that Ninj1 is important for the survival of preOCs. Finally, analysis of publicly available microarray data sets revealed a potent correlation between high NINJ1 expression and destructive bone disorders in humans. Our data indicate that Ninj1 plays an important role in bone homeostasis by enhancing the survival of preOCs.https://doi.org/10.1038/s12276-018-0201-3 |
| spellingShingle | Sung-Jin Bae Min Wook Shin Taekwon Son Hye Shin Lee Ji Soo Chae Sejin Jeon Goo Taeg Oh Kyu-Won Kim Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts Experimental and Molecular Medicine |
| title | Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| title_full | Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| title_fullStr | Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| title_full_unstemmed | Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| title_short | Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| title_sort | ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts |
| url | https://doi.org/10.1038/s12276-018-0201-3 |
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