{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300884/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300884"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Endothelial PIEZO1 activation impairs osteogenesis via GREM1-mediated inhibition of BMP signaling [MC3T3_RNA-seq]","description":"The mechanosensitive ion channel PIEZO1 has emerged as a key regulator of vascular and skeletal biology. Here, we show that systemic activation of PIEZO1 using the chemical agonist Yoda1 in 3-week-old mice disrupts bone homeostasis by impairing type H endothelial cells and inhibiting osteogenic differentiation. In vivo, Yoda1 treatment significantly reduced the abundance of CD31hiEMCNhi type H vessels and altered trabecular bone microarchitecture without affecting total bone mass. In vitro, Yoda1 inhibited osteogenic gene expression and alkaline phosphatase activity in MC3T3-E1 preosteoblasts. Transcriptomic analysis of Yoda1-treated human bone microvascular endothelial cells (hBMECs) revealed a shift from an angiogenic H-type to a quiescent L-type, accompanied by upregulation of BMP signaling antagonists, particularly GREM1. Functional assays confirmed that GREM1 secreted from Yoda1-stimulated endothelial cells suppresses BMP4-induced osteoblast differentiation via paracrine signaling. Together, these findings uncover a novel endothelial-to-osteoblast regulatory axis mediated by PIEZO1-GREM1-BMP4 signaling, and underscore the context-dependent effects of PIEZO1 activation on bone regeneration.","dates":{"publication":"2026/06/26"},"accession":"GSE300884","cross_references":{"GSM":["GSM9071091","GSM9071092","GSM9071090","GSM9071095","GSM9071096","GSM9071093","GSM9071094","GSM9071089"],"GPL":["34290"],"GSE":["300884"],"taxon":["Mus musculus"]}}