UMMS Affiliation
RNA Therapeutics Institute
Publication Date
2019-01-15
Document Type
Article
Disciplines
Cell Biology | Cells | Developmental Biology | Molecular Biology
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.
Keywords
osteoclasts, development, Ninjurin1, Ninj1
Rights and Permissions
Copyright The Author(s) 2019. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any mediumor format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changesweremade. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s12276-018-0201-3
Source
Exp Mol Med. 2019 Jan 16;51(1):7. doi: 10.1038/s12276-018-0201-3. Link to article on publisher's site
Journal/Book/Conference Title
Experimental and molecular medicine
Related Resources
PubMed ID
30700695
Repository Citation
Bae S, Shin MW, Son T, Lee HS, Chae JS, Jeon S, Oh GT, Kim K. (2019). Ninjurin1 positively regulates osteoclast development by enhancing the survival of prefusion osteoclasts. Open Access Articles. https://doi.org/10.1038/s12276-018-0201-3. Retrieved from https://escholarship.umassmed.edu/oapubs/3751
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cell Biology Commons, Cells Commons, Developmental Biology Commons, Molecular Biology Commons