Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endothelial PIEZO1 activation impairs osteogenesis via GREM1-mediated inhibition of BMP signaling [MC3T3_RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE300884 | GEO | 2026/06/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Endothelial PIEZO1 activation impairs osteogenesis via GREM1-mediated inhibition of BMP signaling [hBMEC_RNA-seq]

Project 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.

2026-06-26 | GSE300883 | GEO

Endothelial cell-secreted bone targeting exosomes promote angiogenesis coupling with osteogenesis via the PERK-ATF4-CRELD2 pathway

Project description:The role of endoplasmic reticulum (ER) stress in bone metabolism and the management of associated diseases has garnered significant interest. However, its role in regulating bone homeostasis and skeletal development remains largely unclear. Osteoblast development and bone formation are enhanced by a particular subtype of CD31hi endomucinhi (CD31hiEMCNhi) endothelium. However, it is still unclear how endothelial exosomes contribute to the production of CD31hiEMCNhi endothelium and bone formation. This research revealed that human umbilical vein endothelial cells (HUVECs)-exosomes (Exos) enhanced the formation of osteoblast and angiogenic effects in vitro. Furthermore, in mice treated with HUVECs-Exos, osteoblast production, and CD31hiEmcnhi vessels were significantly increased. The mechanism by which HUVECs-Exos CRELD2 improved angiogenesis coupling with osteogenesis involved triggering the PERK-ATF4-CRELD2 pathway's ER stress. As a result, HUVECs-Exos CRELD2 may be used as a potential bone metabolic disease nanodrug.

2025-01-30 | GSE288030 | GEO

Single-cell RNA-seq analysis reveals two specific endothelial cells promote fracture healing

Project description:Recent studies have identified a bone vessel subtype of CD31hi endomucinhi (CD31hiEMCNhi) endothelium that positively promotes bone formation. However, it remains unknown how CD31hiEMCNhi endothelium participate in the healing of fractures. Here we find that CD31hiEMCNhi endothelial cells increase significantly during fracture healing by single-cell profiling. Furthermore, CD31hiEMCNhi endothelial cells can balance membrane and cartilage osteogenesis in this progress. Moreover, two different types of CD31hiEMCNhi endothelial cells were found in this progress, One of these endothelial cells tends to deliver molecules that induce mesenchymal stem cells differentiate into osteoblast. The other one tends to deliver inflammatory factors associated with osteoclasts. Thus, our study indicates that two specific endothelial cells promote fracture healing and may represent a potential treatment for promoting fracture healing.

2021-11-01 | GSE132884 | GEO

The pivotal role of the Hes1–Piezo1 pathway in the pathophysiology of glucocorticoid-induced osteoporosis [human_GIOP]

Project description:Glucocorticoid-induced osteoporosis (GIOP) lacks fully effective treatments. This study investigated the role of Piezo1, a mechanosensitive ion channel component 1, in GIOP. We found reduced Piezo1 expression in cortical bone osteocytes from patients with GIOP and a GIOP mouse model. Yoda1, a Piezo1 agonist, enhanced the mechanical stress response and bone mass and strength, which were diminished by dexamethasone (DEX) administration in GIOP mice. RNA sequencing revealed that Yoda1 elevated Piezo1 expression by activating the key transcription factor Hes1, followed by enhanced CaM kinase II and Akt phosphorylation in osteocytes. This improved lacuno-canalicular network and reduced sclerostin production and receptor activator of nuclear factor kappa beta/osteoprotegerin ratio, which were mitigated by DEX. Comparative analysis of mouse models and human GIOP cortical bone revealed downregulation of mechano-stimulated osteogenic factors, such as osteocrin, and cartilage differentiation markers in osteoprogenitor cells. In human periosteal-derived cells, DEX suppressed differentiation into osteoblasts, but Yoda1 rescued this effect. Our findings suggest that reduced Piezo1 expression and activity in osteocytes and periosteal cells contribute to GIOP, and Yoda1 may offer a novel therapeutic approach by restoring mechanosensitivity.

2024-12-18 | GSE276529 | GEO

The pivotal role of the Hes1–Piezo1 pathway in the pathophysiology of glucocorticoid-induced osteoporosis

2024-12-18 | GSE276391 | GEO

Transgene-free generation of long-term hematopoietic stem cells

Project description:Analyze the role of cyclic stretch and Yoda1-mediated Piezo1 activaiton in the endothelial-to-hematopoietic transition

2025-06-02 | GSE164725 | GEO

MicroRNA-497~195 cluster regulates angiogenesis during coupling with osteogenesis via maintaining endothelial Notch and HIF-1α activity

Project description:Recently a specific vessel subtype in bone, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. To figure out underlying mechanism of type H vessels generation, we isolated CD31hiEmcnhi and CD31loEmcnlo endothelial cells from one months old mice and perfermed microarrays to detail the microRNA expression. we identified that the miR-497~195 cluster was strongly expressed in CD31hiEmcnhi endothelial cells.

2017-06-30 | GSE95196 | GEO

Piezo1 channels restrain ILC2s and regulate the development of airway hyperactivity [yoda1]

Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.

2024-02-20 | GSE255881 | GEO

Piezo1 channels restrain ILC2s and regulate the development of airway hyperactivity [piezo1KO]

2024-02-20 | GSE255882 | GEO

Expression Data from ATDC5 cells treated with Yoda1

Project description:Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. Chondrocytes can potentially perceive mechanical stimuli via Piezo channels. We investigated the effect of the Piezo1 agonist Yoda1 on chondrocyte-like ATDC5 cells. We used microarray analysis to detail the global gene expression of ATDC5 cells in response to 6 hours of treatment with 5µM Yoda1.

2024-02-28 | GSE230071 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data