MiRNA profiling during fracture repair
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE76197 | GEO | 2016/04/05
SECONDARY ACCESSION(S): PRJNA306611
REPOSITORIES: GEO
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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
Project description:The association between DM and impaired fracture healing including delayed union and nonunion has been documented in clinical and experimental settings. We examine miRNA expression specific for impaired fracture healing in diabetic rat.
2017-01-15 | GSE76365 | GEO
Project description:During endochondral fracture repair, a myriad of biochemical and phenotypic changes occur at the chondro-osseuous junction that regulate cartilage to bone conversion. Osteogenic and angiogenic factors have long been studied for accelerating fracture repair. In our concise study, we focused on the neurotrophic factor nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TRKA) as understudied therapeutic targets for accelerating endochondral fracture repair. We first characterized endogenous expression of NGF and TRKA during endochondral repair of tibial fractures. We then analyzed gene expression data from β-NGF stimulated hypertrophic cartilage and observed a promotion in endochondral ossification associated markers. Additional gene ontology analyses revealed promotion of genes associated with Wnt activation, PDGF binding, and integrin binding. Subsequent histological analyses of in vivo samples confirmed Wnt activation following local β-NGF injections via reporter mice. Finally, we tested the therapeutic efficacy of local β-NGF injections in mice, which resulted in a decrease of cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate the ability for β-NGF to promote endochondral fracture repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during endochondral ossification.
2020-12-22 | GSE150092 | GEO
Project description:Fracture non-union is a complex clinical condition affecting many patients worldwide; however, known risk factors alone cannot help in predicting individual risk of progressing towards healing complications. The identification of novel biomarkers in the serum of fracture patients is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) that could correlate to the process of fracture healing. Toward this aim, serum of fracture patients and healthy volunteers was screened by RNA sequencing to identify differentially expressed miRNA at different times after injury. The results were correlated to miRNA that were found to be differentially secreted in the conditioned medium of human bone marrow mesenchymal stromal cells (BMSCs) during in vitro osteogenesis.
2024-06-02 | GSE217879 | GEO
Project description:miRNA as biomarkers for fracture healing
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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:Interleukin-6 (IL-6) is highly upregulated in response to skeletal injury, suggesting it plays a role in the inflammatory phase of fracture repair. However, the impact of IL-6 on successful repair remains incompletely defined. Therefore, we investigated IL-6 in fracture repair using 12-week old IL-6 global knockout mice (IL-6 KO) and two models of fracture repair: full fracture and stress fracture. Callus formation 14 days after full fracture did not differ between IL-6 knockout mice and controls. However, IL-6 KO mice had an enhanced response 7 days after stress fracture compared to control, with increased callus (p=0.020) and bone formation (p=0.045). IL-6 KO did not alter the recruitment of neutrophils or macrophages to the stress fracture callus. IL-6 KO also did not alter the number of osteoclasts in the stress fracture callus. Based on RNA-seq, IL-6 KO resulted in only modest alterations to the gene expression at early time points after stress fracture. Wnt1 was more highly upregulated in IL-6 KO callus at both day 1 (fold change 12.5 vs. 5.7) and day 3 (fold change 4.7 vs. 1.9) compared to controls. Finally, using tibial compression to induce bone formation, we found that IL-6 KO directly impacted osteoblast function, increasing the propensity for woven bone formation. Herein, we report that IL-6 knockout enhanced formation of callus and bone following stress fracture injury, likely through direct action on the osteoblast’s ability to produce woven bone. This suggests a novel role of IL-6 as a suppressor of intramembranous bone formation.
2021-01-12 | GSE157460 | GEO
Project description:Sprague-Dawley rats were placed on an ethanol-containing or pair-fed Lieber and DeCarli diets for 4 wks prior to surgical fracture. Following insertion of a medullary pin, a closed mid-diaphyseal fracture was induced using a Bonnarens and Einhorn fracture device. At 3 days post-fracture, the region of the fracture calluses were harvested from the right hind-limb. RNA was extracted and microarray analysis was conducted against the entire rat genome to study the effects of alcohol-consumption on the fracture healing. The experiments were on four rat subjects, i.e., pair-fed rats with subsequent surgical fracture or no surgical fracture, and alcohol-fed rats with subsequent surgical fracture or no surgical fracture. Each rat subject described above has three replicates so 6 kinds of pairing can be made and each pairing has a dye-swap replicate (thus, a total 12 array experiments). The focus of this study is on the pair-fed fracture subject vs. alcohol-fed fracture subject.
2011-05-01 | E-GEOD-16003 | biostudies-arrayexpress
Project description:Bone fracture repair represents an important clinical challenge with nearly 1 million non-union fractures occurring annually in the U.S. Gene expression differs between non-union and healthy repair, suggesting there is a pattern of gene expression that is indicative of optimal repair. Despite this, the gene expression profile of fracture repair remains incompletely understood. In this work, we used RNA-seq of two well-established murine fracture models to describe gene expression of intramembranous and endochondral bone formation. We used top differentially expressed genes, enriched gene ontology terms and pathways, callus cellular phenotyping, and histology to describe and contrast these bone formation processes across time. Intramembranous repair, as modeled by ulnar stress fracture, and endochondral repair, as modeled by femur full fracture, exhibited vastly different transcriptional profiles throughout repair. Stress fracture healing had enriched differentially expressed genes associated with bone repair and osteoblasts, highlighting the strong osteogenic repair process of this model. Interestingly, the PI3K-Akt signaling pathway was one of only a few pathways uniquely enriched in stress fracture repair. Full fracture repair involved a higher level of inflammatory and immune cell related genes than did stress fracture repair. Full fracture repair also differed from stress fracture in a robust downregulation of ion channel genes following injury, the role of which in fracture repair is unclear. This study offers a broad description of gene expression in intramembranous and endochondral ossification across several time points throughout repair and suggests several potentially intriguing genes, pathways, and cells whose role in fracture repair requires further study
2020-06-18 | GSE152677 | GEO
Project description:Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. Current therapies aimed at mitigating inflammation or enhancing stem cell function with osteogenic factors yield inconsistent clinical outcomes. To tackle the complexity and heterogeneity of fracture repair process, we performed single-cell RNA sequencing and revealed that progenitor cell was one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation ofRbpjkin fracture nonunion.We then validated the interplay between inflammation (via Ikk2ca) and Rbpjkspecifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identifiedRbpjkas a direct target of Dnmt3b. Mechanistically, intrinsic inflammation decreased Dnmt3b expression in progenitor cells, consequently leading toRbpjkupregulation via hypomethylation within its promoter region. We also showed thatDnmt3bloss-of-function mice phenotypically recapitulated the fracture repair defects observed inIkk2camice, whereasDnmt3btransgenic mice alleviated fracture repair defects induced byIkk2ca. Moreover,Rbpjkablation restored fracture repair in bothIkk2camice andDnmt3bloss-of-function mice. Altogether, this work elucidates a common mechanism involving NF-kB/Dnmt3b/Rbpjkaxis within the context of inflamed bone regeneration. Building upon this novel mechanistic insight, we applied local treatment with epigenetically modified progenitor cells in RA mice and showed a functional restoration of bone regeneration under inflammatory condition through an increase in progenitor differentiation potential. These findings underscore the promise of epigenetic-based therapeutic interventions for addressing delayed fracture union and nonunion particularly associated with systemic inflammation.
2024-10-22 | GSE242836 | GEO