Endothelial-to-osteoblast transition in normal mouse bone development
Summary: Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal b...
Main Authors: | , , , , , , , , , , , |
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Elsevier
2023-02-01
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Series: | iScience |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000718 |
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author | Song-Chang Lin Guoyu Yu Yu-Chen Lee Jian H. Song Xingzhi Song Jianhua Zhang Theocharis Panaretakis Christopher J. Logothetis Yoshihiro Komatsu Li-Yuan Yu-Lee Guocan Wang Sue-Hwa Lin |
author_facet | Song-Chang Lin Guoyu Yu Yu-Chen Lee Jian H. Song Xingzhi Song Jianhua Zhang Theocharis Panaretakis Christopher J. Logothetis Yoshihiro Komatsu Li-Yuan Yu-Lee Guocan Wang Sue-Hwa Lin |
author_sort | Song-Chang Lin |
collection | DOAJ |
description | Summary: Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow– and lung-derived ECs underwent transition to OSBs and mineralization in osteogenic medium. RNA-sequencing revealed GATA family transcription factors were upregulated in EC-OSB hybrid cells and knockdown of GATA3 inhibited BMP4-induced mineralization. Our findings support that EC-to-OSB transition occurs during normal bone development and suggest a new paradigm regarding the endothelial origin of OSBs. |
first_indexed | 2024-04-10T09:30:59Z |
format | Article |
id | doaj.art-77a3dca6b28648a9a8a0ae9927dfae0e |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-04-10T09:30:59Z |
publishDate | 2023-02-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
spelling | doaj.art-77a3dca6b28648a9a8a0ae9927dfae0e2023-02-19T04:26:52ZengElsevieriScience2589-00422023-02-01262105994Endothelial-to-osteoblast transition in normal mouse bone developmentSong-Chang Lin0Guoyu Yu1Yu-Chen Lee2Jian H. Song3Xingzhi Song4Jianhua Zhang5Theocharis Panaretakis6Christopher J. Logothetis7Yoshihiro Komatsu8Li-Yuan Yu-Lee9Guocan Wang10Sue-Hwa Lin11Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USADepartments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding authorDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding authorSummary: Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow– and lung-derived ECs underwent transition to OSBs and mineralization in osteogenic medium. RNA-sequencing revealed GATA family transcription factors were upregulated in EC-OSB hybrid cells and knockdown of GATA3 inhibited BMP4-induced mineralization. Our findings support that EC-to-OSB transition occurs during normal bone development and suggest a new paradigm regarding the endothelial origin of OSBs.http://www.sciencedirect.com/science/article/pii/S2589004223000718Biological sciencesCell biologyCancer |
spellingShingle | Song-Chang Lin Guoyu Yu Yu-Chen Lee Jian H. Song Xingzhi Song Jianhua Zhang Theocharis Panaretakis Christopher J. Logothetis Yoshihiro Komatsu Li-Yuan Yu-Lee Guocan Wang Sue-Hwa Lin Endothelial-to-osteoblast transition in normal mouse bone development iScience Biological sciences Cell biology Cancer |
title | Endothelial-to-osteoblast transition in normal mouse bone development |
title_full | Endothelial-to-osteoblast transition in normal mouse bone development |
title_fullStr | Endothelial-to-osteoblast transition in normal mouse bone development |
title_full_unstemmed | Endothelial-to-osteoblast transition in normal mouse bone development |
title_short | Endothelial-to-osteoblast transition in normal mouse bone development |
title_sort | endothelial to osteoblast transition in normal mouse bone development |
topic | Biological sciences Cell biology Cancer |
url | http://www.sciencedirect.com/science/article/pii/S2589004223000718 |
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