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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:iScience
Subjects:
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.
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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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AT xingzhisong endothelialtoosteoblasttransitioninnormalmousebonedevelopment
AT jianhuazhang endothelialtoosteoblasttransitioninnormalmousebonedevelopment
AT theocharispanaretakis endothelialtoosteoblasttransitioninnormalmousebonedevelopment
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