Periosteum Signatures of Delayed Fracture Healing in Type 2 Diabetes at Single-Cell Resolution
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PROVIDER: PRJNA1186159 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Periosteum is highly involved in bone generation. We used single cell RNA sequencing(scRNA-seq) to analyze the heterogenity of periosteum from db/+ and db/db mice, fractured or post-fractured, and the homology of periosteum from mice and human.
2025-07-31 | GSE281902 | 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: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.
2013-11-27 | GSE45156 | GEO
Project description:Profiling of miRNA expressions comparing standard fracture healing models with nonunion models in rats 12w, male, Sprague–Dawley rats were used in this study. Animals were randomized to receive either a surgical treatment that has been shown to produce a nonunion or to a standard stabilized closed femoral shaft fracture that is known to successfully heal. The details of these procedures have been previously described. Briefly, to produce standard healing models, a 1.2-mm diameter K-wire was inserted retrograde into the right femoral intramedullary canal and a closed transverse femoral shaft fracture was produced using a three-point bending apparatus with a drop weight . To produce the nonunion, the fractured site was additionally exposed, and the periosteum was cauterized circumferentially for a distance of 2 mm on each side of the fracture . Five animals from each group were euthanized on post-fracture day 14 for microarray analysis.
2015-09-03 | E-GEOD-55088 | 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:The association between DM and impaired fracture healing including delayed union and nonunion has been documented in clinical and experimental settings. We examine mRNA expression specific for impaired fracture healing in diabetic rat.
2017-01-15 | GSE76364 | 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:Bone fracture healing is a complex and dynamic processhat requires a detailed understanding of the cellular interactions crucial for successful tissue regeneration. We employs optimized spatial transcriptomics to precisely delineate the locations and interactions of these cells within a mouse femur fracture model at day 0 before fracture and days 5, 15 post-fracture. We improved RNA quality significantly by optimizing our decalcification method using Morse's solution, coupled with the use of the Visium CytAssist platform and integrated analyses through the Seurat, CARD, and Monocle frameworks. This approach allowed us to accurately localize critical cell populations, such as periosteum progenitor cells, and identify pivotal transcription factors that regulate their activation and differentiation into chondrocytes or osteogenic cells. We particularly focused on the transformation from mesenchymal progenitor cells (MPCs) to regenerative MPCs (rMPCs), revealing how these cells recruit macrophages near the fracture line during early healing stages and their involvement in fracture healing. Furthermore, using CellChat, we explored potential receptor-ligand pathways that mediate these cellular interactions. This spatial-temporal mapping and molecular characterization substantially deepen our understanding of the cellular and molecular processes involved in fracture healing, highlighting spatial transcriptomics as a robust approach for elucidating the fundamental mechanisms governing bone regeneration.
2025-05-25 | GSE297119 | GEO
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:Recent studies have identified B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation. However, it remains unknown how B cells participate in the healing of fractures. Here we find that B cells decrease significantly during fracture healing and returned to normal levels after that by single-cell profiling. Furthermore, we found that exosomes derived from B cells inhibited the differentiation of osteoblasts and osteoclasts in vitro. Additionally, injection of these exosomes in mice delayed fracture healing. Thus, maintaining low B cell levels in the bone marrow microenvironment promotes fracture healing.
2021-11-01 | GSE142786 | GEO