First Author | Lin SC | Year | 2023 |
Journal | iScience | Volume | 26 |
Issue | 2 | Pages | 105994 |
PubMed ID | 36798441 | Mgi Jnum | J:333335 |
Mgi Id | MGI:7436997 | Doi | 10.1016/j.isci.2023.105994 |
Citation | Lin SC, et al. (2023) Endothelial-to-osteoblast transition in normal mouse bone development. iScience 26(2):105994 |
abstractText | 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. |