MRNA transcriptome analysis of bone in a mouse model of implant-associated Staphylococcus aureus osteomyelitis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA701190 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13675587_1.fastq.gz | Fastqsanger.gz | |||
| SRR13675587_2.fastq.gz | Fastqsanger.gz | |||
| SRR13675588_1.fastq.gz | Fastqsanger.gz | |||
| SRR13675588_2.fastq.gz | Fastqsanger.gz | |||
| SRR13675589_1.fastq.gz | Fastqsanger.gz |
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Project description:Objective: To investigate the molecular pathogenesis of bone with implant-associated osteomyelitis (IAOM) in early and chonic stages. Methods: After a 2 mm sterile stainless pin (0.3 mm in diameter) was inserted into the bone marrow cavity, 2 μl S. aureus solution at 1 × 10e6 CFU/ml was slowly injected into the bone marrow cavity using a micro-syringe to create IAOM mice while only an equal volume of sterile PBS to create controls. Transcriptomic sequencing was performed on day 3 and 14 post-operation, respectively. Differential expression analyses of IAOM_3D vs Ctrl_3D and of IAOM _14D vs Ctrl_14D were performed using the DESeq2 R package (1.16.1); P-values were adjusted using the Benjamini and Hochberg’s approach to control the false discovery rate. The genes with an adjusted P-value < 0.05 and |log2 (Fold Change)| > 1 were recognized as differentially expressed genes (DEGs). GO, KEGG and PPI analysis of DEGs were performed to identify key genes. Results: Differential expression analyses detected a total of 101 DEGs, among which 96 were up-regulated and 5 down-regulated in the femur, when the IAOM and control groups were compared by day 3 post-infection. The number of DEGs significantly increased up to 1,702 by day 14 post-operation, with 1,065 up-regulated and 637 down-regulated in the IAOM femurs compared with controls. Further GO, KEGG and PPI analyses of DEGs suggested that IL-6, CXCL10, IFN-γ and CXCL9 were associated with early development of IAOM. Conclusions: Our study has revealed transcriptomic characteristics of IAOM and suggested that IL-6, CXCL10, IFN-γ and CXCL9 might play an important role in the early stage of IAOM.
2021-02-11 | GSE166522 | GEO
Project description:We aimed to elucidate the mechanism of IL-27/ IL-27 receptor signaling effects on S. aureus osteomyelitis via gene expression studies.
2021-03-16 | GSE168896 | GEO
Project description:To explore how APOE functions in the mechanism of regulation of cholesterol metabolism during S. aureus osteomyelitis, we established S. aureus osteomyelitis models in WT mice and APOE knockout mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of bone marrow from mice mentioned above at day 7 after operation.
2023-07-09 | GSE227521 | GEO
Project description:Biphasic effects of pleiotropic cytokine IL-27 during Staphylococcus aureus implant-associated osteomyelitis
| PRJNA714525 | ENA
Project description:The main reservoir for Staphylococcus aureus osteomyelitis is the bone tissue where this pathogen can persist and form small colony variants for long periods within osteoblasts and osteocytes. Recently the osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here we investigated the intrinsic relation between S. aureus and both bone cells during infection. The infection of osteoblasts and osteocytes by this pathogen generates the functional bifurcation of these cells into two different responders. Whereas osteoblasts are able to induce a strong antimicrobial respond, the osteocytes trigger signals to recruit immune cells and enhance the inflammation. Moreover, we found that extracellular signals from osteocytes enhance the intracellular bacterial clearance on osteoblasts but not on osteocytes. Even that both cells contain TLR2, the main toll receptor responsible of S. aureus recognition, only osteoblasts were able to increase its expression after infection. Although the expression of TLR2 was not altered in osteocytes, these cells secrete higher lipid mediators and cytokines than osteoblasts. In addition, we found by proteomic analysis that the reduced intracellular bacterial killing of osteocytes is related to a low expression of antimicrobial peptides and reactive oxygen species (ROS) in these cells. Our results suggest that osteocytes contribute to the high inflammation observed in osteomyelitis and at the same time, provide the main niche for S. aureus persistence due to their poor intracellular antimicrobial response. Collectively, these findings reveal the roles of bone cells upon S. aureus infection and provide new insight on the treatment failure of osteomyelitis.
2022-08-02 | PXD029440 | Pride
Project description:Bone transport distraction osteogenesis (DO) is one of the most successful surgery-driven endogenous tissue regeneration approaches for the treatment of large bone defects. However, prolonged consolidation, docking site nonunion, and pin tract infection remain challenging complications. Here, we engineered an osteoinductive, biodegradable intramedullary (IM) implant for sustained release of bone morphogenetic protein-2 (BMP-2) as an adjunctive therapy of bone transport to address the clinical challenges. A hybrid tissue engineering construct (HyTEC) technique was developed to enable sustained release of BMP-2 in a broad range. 100% bony fusion was achieved in the IM implants incorporating with 2 μg and 6 μg BMP-2 as early as 34 days after bone transport surgeries in the management of 8-mm femoral defect. Load bearing was restored 55 days after surgeries when the fixator was removed. Eluting BMP-2 from the IM implants accelerates bone formation and angiogenesis at early phase, and increase mineralization at late phase, especially at the docking sites, leading to early bony bridging. Moreover, no pin tract infection but seamless integration could be found in the 2 μg and 6 μg BMP-2 treated groups. Surgical control and IM implant showed high proportion of non-union and pin tract infections. 2 μg BMP-2 delivered by collagen sponge or 0.5 μg BMP-2-laden IM implant did not induce bone regeneration effectively, resulting in some non-unions and infections. A presence of bacteria of fecal origin in the infection sites was identified. In conclusion, this osteoinductive IM implant holds great promise in revolutionizing bone transport DO technique in the management of bone defect by accelerating bone regeneration and mitigating complications.
2023-06-09 | GSE200518 | GEO
Project description:To investigate the transcriptomic profile difference between LEPR cells in peri-implant fibrous tissue and peri-implant bone
2024-03-21 | GSE227869 | GEO
Project description:Background
This work focuses on the computational modelling of osteomyelitis, a bone pathology caused by bacteria infection (mostly Staphylococcus aureus). The infection alters the RANK/RANKL/OPG signalling dynamics that regulates osteoblasts and osteoclasts behaviour in bone remodelling, i.e. the resorption and mineralization activity. The infection rapidly leads to severe bone loss, necrosis of the affected portion, and it may even spread to other parts of the body. On the other hand, osteoporosis is not a bacterial infection but similarly is a defective bone pathology arising due to imbalances in the RANK/RANKL/OPG molecular pathway, and due to the progressive weakening of bone structure.
Results
Since both osteoporosis and osteomyelitis cause loss of bone mass, we focused on comparing the dynamics of these diseases by means of computational models. Firstly, we performed meta-analysis on a gene expression data of normal, osteoporotic and osteomyelitis bone conditions. We mainly focused on RANKL/OPG signalling, the TNF and TNF receptor superfamilies and the NF-kB pathway. Using information from the gene expression data we estimated parameters for a novel model of osteoporosis and of osteomyelitis. Our models could be seen as a hybrid ODE and probabilistic verification modelling framework which aims at investigating the dynamics of the effects of the infection in bone remodelling. Finally we discuss different diagnostic estimators defined by formal verification techniques, in order to assess different bone pathologies (osteopenia, osteoporosis and osteomyelitis) in an effective way.
Conclusions
We present a modeling framework able to reproduce aspects of the different bone remodeling defective dynamics of osteomyelitis and osteoporosis. We report that the verification-based estimators are meaningful in the light of a feed forward between computational medicine and clinical bioinformatics
Model is encoded by Ruby and submitted and curated to BioModels by Ahmad Zyoud
2024-09-02 | BIOMD0000000923 | BioModels
Project description:Peri-implant fibrosis is one of the most common reasons for implant failure and surgical revision after prosthetic joint replacement. This type of surgical revisionis associated with substantial additional morbidity and healthcare costs. However, the cellular and molecular mediators of peri-implant fibrosis remain unclear. Here, we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of leptin receptor-expressing(LEPR+) cells and that these LEPR+cells are necessary and sufficient to both generate and maintain peri-implant fibrotic tissue. Genetic ablation of LEPR+cells prevents peri-implant fibrosis, and implantation of LEPR+cells from peri-implant fibrotic tissue is sufficient to induce fibrosis in secondary hosts. We further identify adhesion G protein-coupled receptorF5 (ADGRF5) as a crucial mediator of the fibrotic response by LEPR+cells, as conditional deletion of ADGRF5 in LEPR+cells attenuates peri-implant fibrosis while augmenting peri-implant bone formation. Finally, we demonstrate that inhibition of ADGRF5 by intra articular or systemic administration of neutralizing anti-ADGRF5prevents and reverses peri-implant fibrosis. Thus, pharmaceutical agents that inhibit the ADGRF5 pathway inLEPR+cells may represent a new approach to prevent and treat peri-implant fibrosis.
2024-03-10 | GSE227128 | GEO
Project description:High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis infection
| PRJEB6003 | ENA