Mus musculus strain:C57bl6
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA980270 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24848556_1.fastq.gz | Fastqsanger.gz | |||
| SRR24848556_2.fastq.gz | Fastqsanger.gz | |||
| SRR24848557_1.fastq.gz | Fastqsanger.gz | |||
| SRR24848557_2.fastq.gz | Fastqsanger.gz | |||
| SRR24848558_1.fastq.gz | Fastqsanger.gz |
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Project description:Aseptic loosening represents a significant factor contributing to joint replacement failure, primarily associated with diminished bone formation and heightened osteoclast-induced osteolysis. Here, a natural polymer-based injectable hydrogel that encapsulates irisin protein (referred to as I-OG hydrogel) is reported. The hierarchical cross-linked structure of the I-OG hydrogel confers favorable mechanical properties, desirable self-healing ability, and acceptable injectability and, more importantly, sustains continuous release of the protein at the interface between the bone and implant prosthesis. The I-OG hydrogel effectively fills the gap between the titanium pin and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, which outcome confirms the occurrence of irisin protein's slow-release process and its inhibitory effect on osteolysis. Mechanistically, our in vitro experiments demonstrated that irisin released from the I-OG hydrogel upregulates the Wnt/β-catenin signaling pathway in bone marrow stromal cells (BMSCs) through integrin αV, while concurrently downregulating the NF-κB (P65) signaling pathway in osteoblasts. These molecular events ultimately promote osteogenic differentiation and inhibit osteoclast activation. Collectively, our findings establish that the I-OG hydrogel effectively counteracts aseptic loosening by resisting osteolysis caused by titanium particles and enhancing periprosthetic bone formation, and offers promising prospects for the treatment of aseptic loosening in prosthetic implants.
2023-06-17 | GSE234863 | GEO
Project description:The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear-particle induced and septic loosening, as well as to gather new insights into the pathogenesis. 824 genes were differentially expressed with a fold change greater than 2. Among these were Chitinase 1, CD52, Calpain 3, Apolipoprotein, CD18, Lysyl oxidase, Cathepsin D, E-Cadherin, VE-Cadherin, Nidogen, Angiopoietin 1 and Thrombospondin 2, and the differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear-particle induced prosthesis loosening (p=0.001). However, using chitinase activity as a marker for early diagnosis, it has a specificity of 83% and a sensitivity of only 52%, due to a high variability both in the disease and in the control group. Experiment Overall Design: Gene expression profiles were generated from 5 periprosthetic membranes of wear-particle induced and 5 of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n=30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n=54) or for other reasons, serving as control subjects (n=259).
2008-06-15 | E-GEOD-7103 | biostudies-arrayexpress
Project description:The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear-particle induced and septic loosening, as well as to gather new insights into the pathogenesis. 824 genes were differentially expressed with a fold change greater than 2. Among these were Chitinase 1, CD52, Calpain 3, Apolipoprotein, CD18, Lysyl oxidase, Cathepsin D, E-Cadherin, VE-Cadherin, Nidogen, Angiopoietin 1 and Thrombospondin 2, and the differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear-particle induced prosthesis loosening (p=0.001). However, using chitinase activity as a marker for early diagnosis, it has a specificity of 83% and a sensitivity of only 52%, due to a high variability both in the disease and in the control group. Keywords: Tissue type comparison, disease state analysis, search for new biomarkers
2008-01-01 | GSE7103 | GEO
Project description:Wear debris-induced osteolysis, especially titanium (Ti) particles-induced osteolysis, is the most common cause of arthroplasty failure with no effective therapy. Previous studies have suggested that inflammation and impaired osteogenesis are associated with Ti particles -induced osteolysis. Selenium (Se) is an essential trace element in the human body, which forms selenomethionine (Se-Met) in nature, and selenoproteins has strong anti-inflammatory and antioxidant stress effects. In this study, the effects of Se-Met on Ti particles-induced osteolysis were observed and the potential mechanism was explored. We found that exogenous Se-Met relieved osteolysis induced by Ti particles in two animal models and MC3T3-E1 cells. We found that the addition of Se-Met effectively inhibited Ti particle-induced inflammation by regulating ROS-dependent NLRP3 inflammasome activation. These therapeutic effects were abrogated in MC3T3-E1 cells that had received a β-catenin antagonist, suggesting that Se-Met alleviates inflammatory osteolysis via the β-catenin signaling pathway. Collectively, these findings indicated that Se-Met may serve as a potential therapeutic agent for treating Ti particle-induced osteolysis.
2023-08-09 | GSE236911 | GEO
Project description:Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process occurs when host macrophages recognize the implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made on understanding molecular responses of macrophage to implant particles, pathways/signals initiating osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanism in pathogenesis of osteolysis and aid in identifying molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to UHMWPE particles of the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, TNFSF15 and CCL20 were further characterized as molecular targets involved pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implant and bone tissue.
2019-05-06 | GSE104589 | GEO
Project description:Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. Microporous hydrogel induced more robust osteogenic differentiation of MSCs and calcium mineral deposition than the nonporous hydrogel confirmed by alkaline phosphatase (ALP) assay and calcium assay. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that the microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.
2024-04-15 | GSE263939 | GEO
Project description:Gene expression profiling in wear-particle induced and infectious endoprosthesis loosening
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Project description:The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. TYMP was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.
2021-06-10 | GSE171542 | GEO
Project description:In 21 patients undergoing revision arthroplasty due to septic or aseptic implant loosening, synovial fluid was collected intraoperatively after opening the joint capsule. In a proteomic MS approach, we wanted now to investigate these synovial fluids for novel proteogenic markers of periprosthetic infections.
2024-05-21 | PXD047507 | Pride
Project description:Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics.The purpose of our study was to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration.
2019-04-17 | PXD012614 | Pride