Fracture Hematoma Micro-Architecture Plays a Crucial Role in Determining Bone Healing Outcomes
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ABSTRACT:
PROVIDER: PRJNA677868 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13040118_1.fastq.gz | Fastqsanger.gz | |||
| SRR13040118_2.fastq.gz | Fastqsanger.gz | |||
| SRR13040119_1.fastq.gz | Fastqsanger.gz | |||
| SRR13040119_2.fastq.gz | Fastqsanger.gz | |||
| SRR13040120_1.fastq.gz | Fastqsanger.gz |
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Project description:The fracture hematoma that forms between the broken fragments of bone serves as a natural fibrin scaffold. However, there is no data regarding the differences between the micro-architectural and biological properties of hematomas formed in normally healing, delayed healing, and non-healing bone defects. Mimicking these three conditions in the rat femur, we demonstrate clear differences in fibrin clot morphology, which directly affect the gene expression pattern. Specifically, RNA-sequencing reveals that the expression of essential osteogenic genes in normally healing defects are significantly up-regulated, whereas in delayed and non-healing defects they are down-regulated. Surprisingly, there were no substantial differences between delayed and non-healing defects. Most importantly, this study demonstrates that the healing outcome has already been determined at the earliest stage of bone healing. These findings could be used to develop biomaterial scaffolds mimicking the micro-architectural properties of normally healing fracture hematoma as a treatment strategy for bone defects. The hypothesis of this study was that the micro-architectural properties of the initially formed hematoma has a significant effect on the regulation of the biological process at the fracture site, which ultimately determines the outcome of bone healing. Three different healing models were investigated - normally healing, delayed healing, and non-healing defects. The results demonstrated that the intrinsic micro-architectural properties of hematomas between those groups varied distinctly in terms of fiber diameter, porosity, and density of the formed fibrin network. Those differences influenced biological responses, as evidenced by a higher expression of osteogenic genes in normally healing compared to delayed and non-healing defects, and the failed activation of BMP-2 in non-healing defects. More importantly, our results demonstrate healing outcomes are already determined at the initial (hematoma) stage of bone healing.
2023-11-01 | GSE161315 | GEO
Project description:Purpose The aim of this study was to determine the fracture hematoma (fxH) proteome after multiple trauma using label free proteomics, comparing two different established surgical treatment strategies. Basic procedures A large animal (sus scrofa), multiple trauma animal model was used in which two different trauma surgical treatment methods were compared: Early Total Care (ETC) versus Damage Control Orthopedics (DCO). fxH was harvested after 72 hours and analyzed using liquid chromatography-tandem mass spectrometry. Protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Main findings The proteome of the early fxH was characterized by immunomodulatory and osteogenic proteins, as well as proteins involved in the coagulation cascade. Distinct, treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodeling. On the other hand, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodeling, as well as proteins related to anti-inflammatory and osteogenic processes. Principal conclusions The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after severe multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regenerative capabilities, and gained insights into regulatory mechanisms of fracture healing after severe trauma.
2024-05-24 | PXD049002 | Pride
Project description:Age-specific alterations of the adaptive immune system include low-grade chronic inflammation, which contributes to the unfavorable outcome of the bone healing process in the elderly. In this work, we aimed to characterize the effect of immune experience and age on cellular phenotype during the early inflammatory phase after bone fracture by using a mouse model which included young, aged, and immune-aged mice 2- and 5-days post osteotomy. Single-cell proteo-genomics quantified thousands of transcriptomes of cells isolated from three different bone regions (fracture hematoma, proximal and distal bone marrow). The fracture hematoma is a very distinct tissue consisting of coagulated blood caused by rupture of adjacent blood vessels, bone marrow influx and cells attracted from the surrounding tissue. The hematoma matures with the healing process and the adjacent bone marrow (proximal and distal to the fracture gap) supports the healing process.
2025-02-25 | GSE273792 | GEO
Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
2024-12-19 | GSE266774 | GEO
Project description:The long-term healing outcome of bone regeneration is known to depend not only on mechanical stability, but also on age and, more importantly, on the overlap of both parameters. Although especially the early healing period determines the healing outcome, it so far remains unclear which factor - mechanical loading or age - dominates this phase and how these factors interact on the molecular level in the early fracture hematoma. We used microarrays to detail the global programme of gene expression underlying the influence of fixation stability in young and old rats and identified distinct classes of regulated genes during this process.
2014-12-31 | GSE53256 | GEO
Project description:Bone regeneration is a highly efficient process allowing scarless healing after injury. Yet, musculoskeletal traumatic injury, when fracture is combined with adjacent muscle injury, alters bone healing leading to fibrous nonunion. The periosteum, the outer layer of bones, is a critical source of skeletal stem/progenitor cells (SSPCs), as well as immune, endothelial and neural cells during bone repair. We generated single nuclei datasets from the injured perioteum and hematoma at day 1-post fracture and from the hematoma/callus at day 5 post-musculoskeletal traumatic injury. These datasets were analyzed in combination with datasets from GSE234451.
2024-10-22 | GSE268276 | GEO
Project description:Bone regeneration is a highly efficient process allowing scarless healing after injury. The periosteum, the outer layer of bones, is a critical source of skeletal stem/progenitor cells (SSPCs), as well as immune, endothelial and neural cells during bone repair. In our study, we generated a single-nuclei atlas of the murine periosteal response to bone fracture. We generated single nuclei datasets from uninjured periosteum and from injured periosteum and hematoma/fracture callus at days 5 and 7 post-injury from wild-type mice.
2024-04-01 | GSE234451 | GEO
Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
| PRJNA1108318 | ENA
Project description:Time-point expression analysis of fractures calluses at 1, 3, and 5 days post-fracture in young and old BALB/c mice. Femur fractures were generated on female c57BI6 mice in triplicate: 8 month old retired breeders (old mice) and 6 week old mice (young mice) were used. 1, 3, and 5 days post-fracture, fracture calluses were dissected and total RNA isolated. Expression profiling was performed using Affymetrix's Mouse Genome 430 2.0 array.
2009-09-01 | E-GEOD-17825 | biostudies-arrayexpress
Project description:To further understand the molecular complexity of fracture repair, we investigated miRNA profiling during the first 14 days post fracture. miRNA expression was investigated at post-fracture days 1, 3, 5, 7, 11, 14 as well as in intact (unfractured bone).
2016-04-05 | E-GEOD-76197 | biostudies-arrayexpress