Single-cell RNA-seq analysis reveals reduction of B cells in the bone marrow promote fracture healing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE142786 | GEO | 2021/11/01
REPOSITORIES: GEO
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Project description:Recent studies have identified a bone vessel subtype of CD31hi endomucinhi (CD31hiEMCNhi) endothelium that positively promotes bone formation. However, it remains unknown how CD31hiEMCNhi endothelium participate in the healing of fractures. Here we find that CD31hiEMCNhi endothelial cells increase significantly during fracture healing by single-cell profiling. Furthermore, CD31hiEMCNhi endothelial cells can balance membrane and cartilage osteogenesis in this progress. Moreover, two different types of CD31hiEMCNhi endothelial cells were found in this progress, One of these endothelial cells tends to deliver molecules that induce mesenchymal stem cells differentiate into osteoblast. The other one tends to deliver inflammatory factors associated with osteoclasts. Thus, our study indicates that two specific endothelial cells promote fracture healing and may represent a potential treatment for promoting fracture healing.
2021-11-01 | GSE132884 | GEO
Project description:In this study, transcriptome sequencing technology was used to detect and analyze the changes in transcriptome of the local injury tissue after fracture. Differentially expressed genes (DEGs) with the high degree were analyzed. Our research results identify some important genes and pathways in the process of fracture healing, and summarize the main characteristics of transcriptome changes in fractures. This laid the foundation for a deeper understanding of the relation between molecular mechanisms and biological processes involved in fracture healing. By identifying the specific time points at which various cellular events occur during the healing process, researchers can gain insights into the complex interplay between cells, signaling pathways, and extracellular matrix components that is required for successful bone healing. This knowledge can inform the development of new therapies and interventions to improve fracture healing outcomes and ultimately enhance the quality of life for patients affected by bone fractures.
2024-03-31 | GSE262132 | GEO
Project description:Fracture healing is a process that involves many cell populations. In this study we characterized gene expression in a subset of cells involved in fracture healing. αSMACreERT2 mice crossed with Ai9 reporter mice that express tdTomato fluorescent protein after Cre-mediated activation were used as an experimental model. αSMA-expressing cells were labeled by tamoxifen administration, then periosteal cells from the tibia were isolated two days later (controls), or tibial fractures were performed and periosteum/soft callus tissue was collected after 2 and 6 days. The tdTomato positive cell population was isolated by flow cytometry, and subjected to microarray analysis. Histology and cell surface marker analysis indicates that αSMACreERT2 labels a mainly mesenchymal population in the periosteum that expands after fracture, and contributes to both osteogenic and chondrogenic elements of the fracture callus. We were therefore able to examine gene expression in a defined population during the early stages of fracture healing. Total RNA was obtained from the tomato positive cells within the periosteal compartment of fractures from αSMACreERT2/Ai9 mice. Control animals were given 2 doses of tamoxifen, and periosteum was collected and labeled cells sorted (8-9 sex-matched mice per group). Fractures were performed after the second dose of tamoxifen, and tomato positive cells from periosteum/callus tissue were isolated 2 and 6 days after fracture (4-8 animals per sample pooled). 3 replicates for each sample are included.
2013-11-27 | E-GEOD-45156 | biostudies-arrayexpress
Project description:Bone fractures, the most common musculoskeletal injuries, heal through three main phases: inflammatory, repair, and remodeling. Around 10% of fracture patients suffer from impaired healing that requires surgical intervention, a huge burden on the healthcare system. The rate of impaired healing increases with metabolic diseases such as obesity-associated hyperglycemia/type 2 diabetes (T2D), an increasing concern given the growing incidence of obesity/T2D. Immune cells play pivotal roles in fracture healing, and obesity/T2D is associated with defective immune-cell functions. However, there is a gap in knowledge regarding the stoichiometry of immune cells that populate the callus and how that population changes during different phases of healing. Here, we used complementary global and single-cell techniques to characterize the repertoire of immune cells in the fracture callus and to identify populations specifically enriched in the fracture callus relative to the unfractured bone or bone marrow. Our analyses identified two clear waves of immune-cell infiltration into the callus: the first wave occurs during the early inflammatory phase of fracture healing, while the second takes place during the late repair/early remodeling phase. Innate immune cells were activated during the early inflammatory phase, but in later phases they returned to homeostatic numbers and activation levels. Of the innate immune cells, distinct subsets of activated dendritic cells were particularly enriched in the inflammatory healing hematoma. In contrast to innate cells, lymphocytes, including B and T cells, were enriched and activated in the callus primarily during the late repair phase. The Diet-Induced Obesity (DIO) mouse, an established model of obesity-associated hyperglycemia and insulin resistance, suffers from multiple healing defects. Our data demonstrate that DIO mice exhibit dysregulated innate immune responses during the inflammatory phase, and defects in all lymphocyte compartments during the late repair phase. Taken together, our data characterize, for the first time, immune populations that are enriched/activated in the callus during two distinct phases of fracture healing and identify defects in the healing-associated immune response in DIO mice, which will facilitate future development of immunomodulatory therapeutics for impaired fracture healing.
2023-09-01 | GSE240390 | GEO
Project description:Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice. To investigate bone healing in osteoporosis, we performed fracture healing studies in wild-type mice (C57BL/6 genetic background) and the low bone mass strains Col1a1-Krm2 and Lrp5-/- (Schulze et al., 2010; Kato et al., 2002). Osteotomy was set in femora of female mice and stabilized by a semi-rigid fixator to allow fast bone healing (RM-CM-6ntgen et al., 2010). 21 days post surgery we analyzed the fracture calli by biochemical/histological methods, as well as micro-computed tomography, and observed impaired fracture healing in Col1a1-Krm2 and Lrp5-/- mice in comparison to wild-type. To identify genes that may be responsible for the impaired healing in osteoporotic mice, we performed microarray analysis of three independent callus samples of each genotype. The callus tissue was taken 10 days after surgery, because extensive bone formation took place at this point.
2013-10-25 | E-GEOD-51686 | biostudies-arrayexpress
Project description:This is a study of femoral fracture healing in female rats 16 weeks old at fracture to compare intramedullary nailing, screw and plate fixation, and sham surgery. The sham surgery group received a surgical exposure of the femur, but no fracture, no plate, and no nail. Samples were collected at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. Each sample is a pool of RNA from three rats from the same surgery group at the same time point after fracture. The middle third of the femur was collected with the cortical bone, fracture callus, and marrow elements. Mid-diaphyseal, simple, transverse fractures were induced by a Gigli saw. The no fracture sample was a time 0 control collected on the day of surgery from intact rats.
2007-11-03 | E-GEOD-1685 | biostudies-arrayexpress
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:This is a study of femoral fracture healing in female rats 16 weeks old at fracture to compare intramedullary nailing, screw and plate fixation, and sham surgery. The sham surgery group received a surgical exposure of the femur, but no fracture, no plate, and no nail. Samples were collected at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. Each sample is a pool of RNA from three rats from the same surgery group at the same time point after fracture. The middle third of the femur was collected with the cortical bone, fracture callus, and marrow elements. Mid-diaphyseal, simple, transverse fractures were induced by a Gigli saw. The no fracture sample was a time 0 control collected on the day of surgery from intact rats. Keywords = rat Keywords = fracture Keywords = plate Keywords = nail Keywords = time Keywords = femur Keywords: time-course
2005-01-01 | GSE1685 | GEO
Project description:mRNA gene expression was measured in intact female Sprague-Dawley rats at 6 (young), 26 (adult) and 52 (older) weeks of age at the time of fracture. Samples were collected at 0, 0.4, 1, 2, 4, and 6 weeks after fracture. RNA from two rats were pooled for each Affymetrix Rat U34A array. Mid-shaft, simple, transverse left femoral fractures were induced after retrograde intramedullary rod fixation with a Bonnarens and Einhorn device. Samples were collected from one third of the femoral length, centered on the fracture site, including the external callus, cortical bone, and marrow elements. Keywords = rat Keywords = fracture Keywords = age Keywords = time Keywords = femur Keywords: other
2004-01-10 | E-GEOD-594 | 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