Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192983 | GEO | 2022/05/20
REPOSITORIES: GEO
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Project description:Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity
| PRJNA794056 | ENA
Project description:This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences
2022-01-26 | GSE192982 | GEO
Project description:There is a need to clarify the role of the meniscus in knee OA which may be aided by the identification of biomarkers that reflect the molecular events involved in the tissue degradation. This is of particular importance in the early stages of the degenerative processes, a crucial phase when it might still be possible to interfere with disease progression before tearing and critical loss of meniscal function occurs. One way to achieve this goal is exploratory proteomics by mass spectrometry (MS), which has the potential to analyse the proteome of complex samples. Thus, our aim was to gain new knowledge about the molecular processes within the human meniscus by comparing the proteomic profiles of both the lateral and medial meniscus from healthy controls, subjects with mild signs of joint degeneration, and patients with end-stage knee OA, using a non-targeted MS approach operating in data-independent acquisition (DIA) mode. For the research purpose six groups were established: medial and lateral menisci from control donors (n=12), medial and lateral menisci from donors with mild signs of joint degeneration (n=13) and medial and lateral menisci from end-stage knee OA patients (n=12).
2024-04-03 | PXD042122 | Pride
Project description:To explore the molecular mechanisms of meniscal degeneration after resection of anterior cruciate ligament and lateral collateral ligament, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential role in the development of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of Wuzhishan minipig was resected at the same time, and the left rear limbs was sham operated. There were significant differences in gene expression between the two groups. A total of 893 differentially expressed genes were identified, of which 537 were upregulated and 356 were downregulated. This study indicated that several molecular mechanisms were implicated in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and offering molecular targets for future therapeutic advances.
2020-12-15 | GSE145402 | GEO
Project description:To investigate the molecular mechanisms governing the transition of skeletal muscle from atrophy to compensatory regeneration and hypertrophy, we employed a mouse model involving hindlimb unloading and subsequent reloading, conducting a comprehensive analysis of global gene expression using RNA-sequencing (RNA-seq). Gastrocnemius muscle samples were obtained from three groups: control mice, mice subjected to 10 days of hindlimb unloading-induced muscle atrophy, and mice reintroduced to normal cage activity for 1 day following the unloading period (reloading).
2023-07-16 | GSE237099 | GEO
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
2023-10-19 | E-MTAB-12390 | biostudies-arrayexpress
Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.
2023-10-19 | E-MTAB-12389 | biostudies-arrayexpress
Project description:Ischemic heart failure after acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a trans-valvular axial-flow pump in the LV and delaying myocardial reperfusion, known as Primary Unloading, limits infarct size by reducing LV wall stress and increasing expression of the cardioprotective cytokine, stromal derived factor 1 alpha (SDF1a). The mechanisms underlying the cardioprotective benefit and sustained effect of Primary Unloading remain poorly understood. We now tested the importance of delayed reperfusion, the functional significance of SDF1a, and the late-term impact on myocardial function and scar size associated with Primary Unloading. Adult male swine were subjected to Primary Reperfusion or Primary Unloading after 90 minutes of left anterior descending artery occlusion. Compared to Primary Reperfusion, 30 minutes of Primary Unloading was necessary and sufficient prior to reperfusion to limit infarct size. Primary Unloading was associated with a global shift in gene expression within the infarct zone favoring cardioprotection. Compared to Primary Reperfusion, Primary Unloading for 30 minutes preserved SDF1a protein levels without changing SDF1a mRNA levels within the infarct zone and further promoted a shift towards anti-apoptotic signaling within the infarct zone. Primary Unloading reduced activity levels of proteases known to degrade SDF1a and blocking the SDF1a receptor, CXCR4, attenuated the cardioprotective effect of Primary Unloading. Primary Unloading further reduced LV scar size, improved cardiac function, limited expression of markers associated with heart failure and maladaptive remodeling within the non-infarct zone 28 days after acute myocardial infarction. In conclusion, we introduce that Primary Unloading for 30 minutes before, not after reperfusion limits infarct size, increases SDF1a levels within the infarct zone, and results in a durable reduction in LV scar size, improved cardiac function, and limits markers of heart failure and maladaptive remodeling 28 days after AMI.
2018-10-25 | GSE108644 | GEO
Project description:A key event during eukaryotic replication termination is the removal of the CMG helicase from chromatin. CMG unloading involves ubiquitylation of its MCM7 subunit and the action of the p97 ATPase. Using a proteomic screen in Xenopus egg extracts, we identified factors that are retained on chromatin when CMG unloading is blocked and identified the E3 ubiquitin ligase CRL2LRR1 and several other potential regulators of termination including a specific p97 complex. We show that CRL2LRR1 recruitment coincides with MCM7 ubiquitylation and occurs only when replisomes converge. In the absence of CRL2LRR1, MCM7 is not ubiquitylated, CMG unloading is inhibited, and many replisome components including DNA pol are retained on DNA. Our data identify CRL2LRR1 as a master regulator of replisome disassembly during vertebrate DNA replication termination.
2017-02-02 | PXD004828 | Pride
Project description:Notch signaling plays essential roles in maintenance of muscle stem cell pool. We found that Notch2, but not Notch1 and Notch3, is expressed in fully differentiated myofibers. To study the specific role of Notch2 in adult myofibers, we generated muscle-specific Notch2-knockout mice. Here, we showed that muscle-specific Notch2 deficiency prevented muscle atrophy induced by hindlimb unloading and diabetes millitus. RNA sequencing analysis revealed that the loss of Notch2 gene in myofibers inhibited gene responses to unloading and diabetes. Especially, several FoxO-target genes and atrogenes were upregulated in wildtype muscles but not in Notch2-deficient muscles by unloading and diabetes. Thus, our characterization of muscle-specific Notch2-knockout mice indicates that Notch2 acts as a regulatory factor of skeletal muscle plasticity and could be a therapeutic target of muscle atrophy.
2022-01-07 | GSE161693 | GEO