Osteocytes regulate skeletal senescence during development
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ABSTRACT:
PROVIDER: PRJNA835705 | ENA |
REPOSITORIES: ENA
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Project description:Osteocytes regulate skeletal senescence during development
| PRJNA836422 | ENA
Project description:To understand the mechanism underlying the bone phenotype in osteocytes ablation mice.
2022-11-21 | GSE202356 | GEO
Project description:As a part of the skeletal system, bone marrow environment also performs vital functions in maintaining the bone homeostasis. To gain an insight into the bone marrow environment change after osteocyte ablation, single cell RNA sequencing (scRNA-seq) was performed
2022-11-21 | GSE202516 | GEO
Project description:The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study, firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients.
2012-05-22 | GSE27372 | GEO
Project description:Cellular senescence disables the proliferation of damaged cells and it is relevant for cancer and aging. Here, we show that cellular senescence occurs during mammalian embryonic development. Specifically, we have focused on the mouse regressing mesonephros and the endolymphatic sac of the inner ear. Senescence is characterized by SAM-NM-2G activity, heterochromatinization, and proliferative arrest. Mechanistically, developmentally-programmed senescence at the mesonephros and endolymphatic sac is strictly dependent on p21, but independent of DNA damage, p53 or other cell cycle inhibitors, and it is regulated by the TGFM-NM-2/SMAD and PI3K/FOXO pathways. Developmentally-programmed senescence is followed by macrophage infiltration and clearance of senescent cells. Abrogation of senescence by p21 deletion is only partially compensated by apoptosis and originates detectable developmental abnormalities. Importantly, high levels of p21 are also associated to the regressing mesonephros and endolymphatic sac in human embryos. These findings place cellular senescence as a relevant morphogenic process during embryonic development. We microdissected mesonephric tubules from senescent (WT) and non-senescent (p21-null) embryos to get information about this new senescence that occurs during embryogenesis.
2013-11-14 | E-GEOD-49108 | biostudies-arrayexpress
Project description:These data examine the total-RNA transcriptome of primary osteocytes in both genders at 4 different stages of skeletal maturation. These stages are prepuberty (4 weeks), post puberty (10 weeks), early skeletal maturation (16 weeks), established skeletal maturation (26 weeks). These data were used to identify temporal changes in gene expression between sexes in the osteocyte network during post natal skeletal growth and maturation.
2020-12-16 | E-MTAB-7447 | biostudies-arrayexpress
Project description:There are three main cell types associated with the skeleton, osteoblasts that bone build, osteoclasts that resorb bone and the osteocytes which among other things control the action of these other effector cell types. In this experiment we compare transcriptome data from bone samples enriched for osteocytes (by removing soft tissue and marrow) and bone samples with the soft tissue removed but the marrow left intact. This identifies genes that are enriched for data when we enrich for osteocytes - highlighting genes enriched for expression in this pivotal skeletal cell type.
2020-03-04 | E-MTAB-5533 | biostudies-arrayexpress
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226007 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226006 | GEO
Project description:Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes. Many studies have investigated the histone modification mechanisms that regulate cellular senescence and aging. In this study, we show that histone lactylation, an identified histone modification that integrates metabolic processes, epigenetic regulation of gene expression and cellular activities in response to internal and external cues, plays a pivotal role in counteracting senescence and mitigating dysfunctions of skeletal muscle in aged mice. Mechanistically, histone lactylation levels markedly decrease during cellular senescence but are restored under hypoxic conditions primarily due to elevated glycolytic activity. The enrichment of histone lactylation at promoters is essential for sustaining the expression of genes involved in the cell cycle and DNA repair pathways, thereby inhibiting cellular senescence. Furthermore, the modulation of enzymes crucial for histone lactylation, including p300 and HDAC1, leads to reduced histone lactylation and accelerated cellular senescence. Consistently, the suppression of glycolysis and the depletion of histone lactylation are also observed during skeletal muscle aging. Running exercise increases the levels of glycolysis and histone lactylation, which in turn upregulate key genes in the DNA repair and proteostasis pathways, thereby helping to preserve the proper function of skeletal muscle. Our study highlights the significant roles of histone lactylation in modulating cellular senescence as well as aging-related tissue function, suggesting that this modification may serve as an innovative biomarker for senescence and provides a promising avenue for antiaging intervention via metabolic manipulation.
2024-05-01 | GSE226005 | GEO