Interleukin-6 (IL-6) deficiency enhances intramembranous osteogenesis following stress fracture in mice
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ABSTRACT:
PROVIDER: PRJNA661340 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12586200_1.fastq.gz | Fastqsanger.gz | |||
| SRR12586200_2.fastq.gz | Fastqsanger.gz | |||
| SRR12586201_1.fastq.gz | Fastqsanger.gz | |||
| SRR12586201_2.fastq.gz | Fastqsanger.gz | |||
| SRR12586202_1.fastq.gz | Fastqsanger.gz |
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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: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: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 the role of IL-6 in two models of fracture repair (full fracture and stress fracture) using 12-week old IL-6 global knockout mice (IL-6 KO) and wild type (WT) littermate controls. Callus morphology and mineral density 14 days after full femur fracture did not differ between IL-6 knockout mice and controls. In contrast, IL-6 KO mice had an enhanced bone response 7 days after ulnar stress fracture compared to WT, with increased total callus volume (p = 0.020) and callus bone volume (p = 0.045). IL-6 KO did not alter the recruitment of immune cells (Gr-1 or F4/80 positive) to the stress fracture callus. IL-6 KO also did not alter the number of osteoclasts in the stress fracture callus. Using RNA-seq, we identified differentially expressed genes in stress fracture vs. contralateral control ulnae, and observed that IL-6 KO resulted in only modest alterations to the gene expression response to stress fracture (SFx). Wnt1 was more highly upregulated in IL-6 KO SFx callus at both day 1 (fold change 12.5 in KO vs. 5.7 in WT) and day 3 (fold change 4.7 in KO vs. 1.9 in WT). Finally, using tibial compression to induce bone formation without bone injury, we found that IL-6 KO directly impacted osteoblast function, increasing the propensity for woven bone formation. In summary, 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.
| S-EPMC8408837 | biostudies-literature
Project description:Transcriptional profiling of intramembranous and endochondral ossification after fracture in mice
| PRJNA640062 | ENA
Project description:Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing
| PRJNA415970 | ENA
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:Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (batch RNA-Seq)
| PRJNA416037 | ENA
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:Over 6.8 million fractures are reported annually in the US, accounting for 20% of all musculoskeletal injuries. Approximately 10% of fractures will experience delayed- or non-union. Parathyroid hormone (PTH) analogs and anabolic osteoporosis therapeutics can stimulate fracture repair in animal models and patients with chronic nonunion. Previous studies have demonstrated that small molecule salt inducible kinase (SIK) inhibitors mimic PTH action in vitro and in vivo. Therefore, we hypothesize that YKL-05-099, a small molecule SIK inhibitor, will accelerate fracture callus osteogenesis.
2024-09-01 | GSE266115 | GEO
Project description:Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (single cell RNA-Seq)
| PRJNA416038 | ENA