Expression data from fracture hematoma tissue of young and old rats after 3days of rigid or semi-rigid fixation of an osteotomy
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE53256 | GEO | 2014/12/31
SECONDARY ACCESSION(S): PRJNA231357
REPOSITORIES: GEO
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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:Some studies have revealed that treating chronic subdural hematoma (CSDH) with drugs is effective; however, the specific mechanism of this process has been seldom discussed. Herein, we sought to identify the potential underlying mechanism of atorvastatin and low-dose dexamethasone for CSDH treatment. We sequenced the hCMEC/D3 cell lines treated with single statin, dexamethasone and low dose dexamethasone after hematoma injuried and statin to find out the key point.
2019-10-22 | GSE139133 | 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.
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Project description:Healing process after connective tissues (CT) injury is complex but important as CT are critical for human moving, and patient outcome of CT injured patients is protracted with high individual variation. Specific markers which could be used for healing prognosis will be great help to monitor patient outcome, and furtherly improve target treatment and patient recovery. Although several common factors like age, gender and body mass index (BMI) were reported to predict ATR healing outcome [references], more specific markers which can be used as predictors of patient outcome after ATR are still lacking. Several biomarkers have been reported to associate with tendon healing, and indicated their relationship with patient outcome(1-4). These results highlight the potential of protein expression detection and analysis for tendon study in general and healing outcome prognosis in particular. Collagen type I (Col1a1) is the main component of Achilles tendon and plays vital role in tendon healing via involving in collagen fibrils production among tendon fibroblasts(5). Higher production of Col1a1 is associated with faster tendon repair(6), previous study on animal model reported the increased Col1a1 synthesis can exert a positive effect on tendon healing[?]. Thus, functional proteins with high impact on Col1a1 can be used not only to improve tendon healing, also can be as targets for healing improvement and outcome prediction. The proteome file of Achilles tendon which is important to increase understanding of tendon healing and help to identify accurate outcome-related biomarkers is however lagged behind. The identification of proteomic profile of Achilles tendon is very much limited in number of proteins and sample size(7-9), and is even few on human. Recent improvement in proteomic assay based on mass spectrometry (MS) made it possible to assemble the proteomic landscape of human tissues(10, 11) with high quality and sensitivity. To characterize the proteomic components in human Achilles tendon, we utilized biopsies from ATR patients with both good and poor 1-year healing outcome. A validated platform including quantitative MS and clinical database was used to identify proteomic landscape and potential bio-predictors of clinical outcome. Our study may provide a more comprehensive landscape of proteins for human Achilles tendon, as well as specific biomarkers which can be used for long term outcome prognosis after ATR.
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Project description:Healing after Achilles tendon rupture (ATR) is protracted with high individual variation and unsatisfactory outcome. Biomarkers prognostic of healing are unknown while physical and mechanical factors are used for predicting long-term healing outcomes in clinics today. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and asess the association with the patient's long term outcomes after ATR. Using quantitative Mass Spectrometry (MS) analysis, 1423 proteins in healing and contralateral healthy Achilles tendon from 28 ATR patients were quantified. Comparing healing and healthy protein profiles, we identified 821 overlapping proteins. Further analysis revealed 390 up-regulated and 17 down-regulated proteins in healing compared to the healthy contralateral side,mainly related to extracellular matrix organization, inflammation, and reduced exocytosis and metabolic pathways. Our analysis based on clinical parameters, identified complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing.Our findings identidied identified prognostic biomarkers and potential therapeutic target for improving tendon or ligament injuries.
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Project description:Rejuvenating Age-impaired Fracture Healing
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Project description:Ageing compromises the mechanical properties of skin, with increased fragility and coincident slowing of the healing process making aged skin susceptible to chronic wounding. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, compounded by regulatory changes, including age-associated hormonal dysregulation. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and chronologically aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing lead to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the ovariectomy model was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, indicative of the role of estrogen-related pathways in ageing. This study offers a coherent picture of the relationship between tissue composition and mechanics, but suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.
2019-03-11 | PXD012753 | Pride
Project description:Ageing compromises the mechanical properties of skin, with increased fragility and coincident slowing of the healing process making aged skin susceptible to chronic wounding. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, compounded by regulatory changes, including age-associated hormonal dysregulation. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and chronologically aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing lead to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the ovariectomy model was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, indicative of the role of estrogen-related pathways in ageing. This study offers a coherent picture of the relationship between tissue composition and mechanics, but suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.
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