Endothelial-to-osteoblast transition in normal mouse bone development
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
Affiliations
Song-Chang Lin
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Guoyu Yu
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yu-Chen Lee
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jian H. Song
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Xingzhi Song
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Jianhua Zhang
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Theocharis Panaretakis
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Christopher J. Logothetis
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Yoshihiro Komatsu
Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USA
Li-Yuan Yu-Lee
Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Guocan Wang
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author
Sue-Hwa Lin
Department 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 author
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.
