Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1108318 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28920000_1.fastq.gz | Fastqsanger.gz | |||
| SRR28920000_2.fastq.gz | Fastqsanger.gz | |||
| SRR28920001_1.fastq.gz | Fastqsanger.gz | |||
| SRR28920001_2.fastq.gz | Fastqsanger.gz | |||
| SRR28920002_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
2024-12-19 | GSE266774 | GEO
Project description:Periosteal expansion is a key process in the early stages of bone fracture repair. The periosteum is typically quiescent, but upon fracture it expands, periosteal cells proliferate and contribute to the formation of a cartilaginous callus . The early expansion of the periosteum is tightly regulated at the transcriptional level. However, the molecular mechanisms behind periosteal expansion are unknown. Here, we show that Yes-Associated Protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) mediate periosteal expansion and periosteal cell proliferation. Bone fracture results in increased numbers of YAP-expressing periosteal cells. Deletion of YAP from Osterix (Osx) expressing periosteal cells impairs early periosteal expansion. Mechanistically, YAP regulates both cell intrinsic and extrinsic transcriptional programs that allow for periosteal expansion. Specifically, we identified Bmp4 as a cell extrinsic factor regulated by YAP, that rescues the impairment of periosteal expansion upon YAP deletion. Together, these data establish YAP mediated molecular mechanisms that allow for periosteal expansion in the early stages of fracture repair.
2025-01-07 | GSE280239 | GEO
Project description:The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of β-catenin. In detail, YAP directly interacts with β-catenin in the nucleus and forms a transcriptional YAP/β-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion.
| S-EPMC9274506 | biostudies-literature
Project description:The periostieum is a fiberous network on the outside of the bones crucial to fracture healing. Here we present our scRNA-seq data from intact and fractured periosteal cells, collected three days after injury, from young adult and aged mice.
2025-05-15 | GSE280914 | GEO
Project description:In China, the incidence of fracture non-unions is relatively high. Impaired endochondral ossification may lead to nonunion due to improper mechanical loading. As a mechanosensitive ion channel protein, Piezo1mediates mechanical transduction and induces calcium inward flow. Our early study showed that the osteogenic and angiogenic capacity of chondrocytes was reduced, if Piezo1 gene was knocked out on chondrocytes. Moreover, the expression of mitochondrion translation related gene LARS2 was signaling increased. Therefore, we hypothesize that the mechanical loading may cause endochondral ossification through the Piezo1- LARS2 signaling pathway. We will use conditioned gene knockout mice and Peizo1 knockdown stable cell line to support the hypothesis. Our goals include investigating the changes of Piezo1 expression during endochondral ossification of femoral fracture healing in mice under mechanical loading; investigating the response of Piezo1 channels on chondrocytes to mechanical stimulation and its role and mechanism in regulating chondrocyte osteogenesis and angiogenesis, maintaining the normal mitochondrial function in vitro; analysing the key molecular and signal network downstream of Piezo1 through the multi-omics techniques; and exploring the response mechanism of Piezo1 under vibrating stimulus. This project aims to study the molecular mechanism of Piezo1-mediated force-biological information transition and its role in endochondral ossification. We hope it provides an effective intervention target for preventing and treating fracture nonunion.
2024-12-19 | GSE242712 | GEO
Project description:Bone regeneration is a highly efficient process allowing scarless healing after injury. The periosteum, the outer layer of bones, is a critical source of skeletal stem/progenitor cells (SSPCs), as well as immune, endothelial and neural cells during bone repair. In our study, we generated a single-nuclei atlas of the murine periosteal response to bone fracture. We generated single nuclei datasets from uninjured periosteum and from injured periosteum and hematoma/fracture callus at days 5 and 7 post-injury from wild-type mice.
2024-04-01 | GSE234451 | GEO
Project description:YAP regulates periosteal expansion in early fracture repair.
| PRJNA1177429 | ENA
Project description:Aged induced periosteal changes during early fracture healing
| PRJNA1181030 | ENA
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 | GSE276391 | GEO
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