Endothelial-to-osteoblast transition in normal mouse bone development
Year: 2023
Type: article
Abstract: 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.
Source: iScience
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Awards: G10598100, G111615301, G1675379494, MD Anderson Cancer Center Prostate Cancer SPORE, G4119534169, G4400572289, A Novel Therapy Targeting Prostate Cancer–Induced Aberrant Bone Formation, G5850682332, G640481018, Regulation of dormancy of metastatic prostate cancer cells by bone microenvironment, Endothelial-to-osteoblast transition in prostate cancer bone metastasis, TARGETING HISTONE LYSINE DEMETHYLASE KDM4A IN NEUROENDOCRINE PROSTATE CANCER., G9000134271
OpenAlex ID: W4318897331