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Investigation of the changes induce by inhibiting mitochondrial respiration on DNA methylation and hydroxymethylation in periosteal cells

ABSTRACT: Investigation of the changes induce by inhibiting mitochondrial respiration on DNA methylation and hydroxymethylation in periosteal cells

PROVIDER: PRJNA814240 | ENA |

REPOSITORIES: ENA

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Investigation of the changes induce by inhibiting mitochondrial respiration on DNA methylation and hydroxymethylation in periosteal cells

Project description:The metabolic changes induced by blocking mitochondrial respiration result in a decrease of 5hmC levels. This experiment aims to further investigate the changes in DNA demethylation induced by Antimycin A treatment using both regular bisulfite- and oxidative bisulfite-chip sequencing.

2022-08-26 | GSE198222 | GEO

YAP regulates periosteal expansion in early fracture repair.

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

Supinoxin Blocks Small Cell Lung Cancer Progression by Inhibiting Mitochondrial Respiration through DDX5

Project description:Supinoxin Blocks Small Cell Lung Cancer Progression by Inhibiting Mitochondrial Respiration through DDX5

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Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

2024-12-19 | GSE266774 | GEO

Sfrp4 is Required to Maintain Ctsk-Lineage Periosteal Stem Cell Niche Function

Project description:The periosteum contains cells which function as a reservoir of stem cells and progenitors and contribute to cortical expansion during growth, cortical bone homeostasis and repair. However, the local or paracrine factors that govern stem cell renewal and differentiation within the periosteal niche remains elusive. Cathepsin K (Ctsk) together with additional cell surface markers marks a subset of stem cells in the periosteum (PSC) which possess self-renewal ability and inducible multipotency. These PSCs produce osteoblasts mediating periosteal bone formation and fracture repair. Sfrp4 is expressed in periosteal Ctsk-lineage cells and using CtskCre mice that are either wild type or Sfrp4-/-, we report here that Sfrp4 deletion decreases the pool of PSCs, impairs their self-renewal, their ability to give rise to their derivatives and their clonal multipotency for differentiation into osteoblasts and chondrocytes in vitro and formation of bone organoids in vivo. Bulk RNA sequencing analysis in Ctsk-lineage PSCs demonstrated that Sfrp4 deletion leads to downregulation of signaling pathways associated with skeletal development, positive regulation of bone mineralization and wound healing. Sfrp4 deletion hampers the Ctsk-lineage PSC response and recruitment after bone injury and leads to an impaired periosteal response. Periosteal Ctsk-lineage cells respond to PTH(1-34) treatment with an increase in the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, bone histomorphometry analysis showed that in the absence of Sfrp4, PTH(1-34)-dependent increase in cortical thickness, periosteal bone formation is markedly impaired.

2024-08-13 | GSE236686 | GEO

Periosteal skeletal stem cells can migrate into the bone marrow and support hematopoiesis after injury [I]

Project description:To investigate the transcriptomic differences between bone marrow mesenchymals stem cells and periosteal skeletal stem cells at steady state, and periosteal skeletal stem cells 72 hours after bone transplantation

2023-01-12 | GSE216824 | GEO

RNA-seq analysis on osteoclasts and periosteal stem cells from control and Prmt5 f/d Ctsk-Cre mice

Project description:To gain insights into the role of Prmt5 in osteoclasts and periosteal stem cells , we performed RNA sequencing (RNA-seq) on osteoclasts and periosteal stem cells from control and Prmt5 f/d Ctsk-Cre mice

2022-05-07 | GSE146872 | GEO

Comparison of periosteal, adipose, and dermal CD146+ human pericytes

Project description:Human pericytes demonstrate multilineage differentiation potential, and their descendants participate in tissue homeostasis and repair. Increasing evidence from developmental biology and tissue engineering suggest that regional specification by tissue of origin exists among human pericytes. Here, we sought to define the differentiation of CD146+ human pericytes from skeletal and soft tissue sources. Uncultured CD146+CD31-CD45- pericytes were derived by fluorescent activated cell sorting from human periosteum, adipose, or dermal tissue. Periosteal CD146+CD31-CD45- cells retained canonical features of pericytes, including cell surface marker expression, multilineage differentiation potential, and paracrine induced tubulogenesis. Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis, while soft tissue pericytes did not in vitro or in vivo. Microarray analysis demonstrated substantive differences between periosteal pericytes in comparison to their soft tissue pericyte counterparts. In sum, skeletal and soft tissue pericytes differ in their relative lineage differentiation potential and ability to form bone. Human tissues were microdissected, digested, and FACS sorted to derived a CD146+CD31-CD45- pericyte population, and cells were expanded in standard growth medium (DMEM, 10% FBS, 1% pen/strep) and nucleic acid isolated at subconfluency

2021-08-01 | GSE118962 | GEO

WAS enhance organohalides respiration

Project description:WAS enhance organohalides respiration

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Supinoxin Blocks Small Cell Lung Cancer Progression by Inhibiting Mitochondrial Respiration through DDX5

Project description:DDX5 is a DEAD-box RNA helicase that is overexpressed and implicated in the progression of several cancers, including small cell lung cancer (SCLC). Our laboratory has demonstrated that DDX5 is essential for the invasive growth of SCLC and mitochondrial respiration. SCLC is an extremely lethal, recalcitrant tumor, and currently lacking effective treatments. Supinoxin (RX 5902), a compound having anti-cancer activity, is a known target of phosphor-DDX5. We now report that Supinoxin inhibits the proliferation of chemo-sensitive and chemo-resistant SCLC lines, H69 and H69AR respectively. Additionally, Supinoxin mitigates both the growth of H69AR xenograft tumors and SCLC PDX tumors in vivo. Finally, we find that Supinoxin inhibits expression of mitochondrial genes and effectively blocks respiration. These studies suggest that Supinoxin functions in anti-tumor progression by reducing cellular energy levels through DDX5.

2025-02-20 | GSE255741 | GEO

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