Periosteum Signatures of Delayed Fracture Healing in Type 2 Diabetes at Single-Cell Resolution
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE281902 | GEO | 2025/07/31
REPOSITORIES: GEO
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Project description:Periosteum Signatures of Delayed Fracture Healing in Type 2 Diabetes at Single-Cell Resolution
| PRJNA1186159 | ENA
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: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:The periostieum is a fiberous network on the outside of the bones crucial to fracture healing. Here we present our scRNA-seq data from intact and fractured periosteal cells, collected three days after injury, from young adult and aged mice.
2025-05-15 | GSE280914 | GEO
Project description:The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched with progenitor cells, including Sca1+ cells, fibroblast colony-forming units, and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that alpha smooth muscle actin (αSMA) identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched with skeletal progenitor cells, and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.
| S-EPMC7906599 | biostudies-literature
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:Bone regeneration relies on the activation of skeletal stem cells (SSCs) that still remain poorly characterized. Here, we show that periosteum contains SSCs with high bone regenerative potential compared to bone marrow stromal cells/skeletal stem cells (BMSCs) in mice. Although periosteal cells (PCs) and BMSCs are derived from a common embryonic mesenchymal lineage, post-natally PCs exhibit greater clonogenicity, growth and differentiation capacity than BMSCs. During bone repair, PCs can efficiently contribute to cartilage and bone, and integrate long-term after transplantation. Molecular profiling uncovers genes encoding Periostin and other extracellular matrix molecules associated with the enhanced response to injury of PCs. Periostin gene deletion impairs PC functions and fracture consolidation. Periostin-deficient periosteum cannot reconstitute a pool of PCs after injury demonstrating the presence of SSCs within periosteum and the requirement of Periostin in maintaining this pool. Overall our results highlight the importance of analyzing periosteum and PCs to understand bone phenotypes.
2018-10-18 | E-MTAB-6417 | biostudies-arrayexpress
Project description:Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3–14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1–14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.
2022-02-15 | GSE182906 | GEO
Project description:Congenital pseudarthrosis of the tibia (CPT) is a severe pediatric disorder affecting children. CPT is characterized by tibial bowing at birth leading to spontaneous fracture and fibrous non-union. Our study showed the presence of biallelic inactivation of the NF1 gene in the periosteum at the pseudarthrosis site. To understand the impact of NF1 mutation on the periosteum, we performed single nuclei RNAseq of pathological periosteum collected from the pseudarthrosis site and of non-pathological periosteum collected from the iliac crest of 3 CPT patients.
2024-07-24 | GSE232516 | GEO
Project description:Delayed healing and nonunion of fractures represent enormous burdens to patients and healthcare systems. There are currently no approved pharmacological agents for the treatment of established nonunions, or for the acceleration of fracture healing, and no pharmacological agents are approved for promoting the healing of closed fractures. Yet several pharmacologic agents have the potential to enhance some aspects of fracture healing. In preclinical studies, various agents working across a broad spectrum of molecular pathways can produce larger, denser and stronger fracture calluses. However, untreated control animals in most of these studies also demonstrate robust structural and biomechanical healing, leaving unclear how these interventions might alter the healing of recalcitrant fractures in humans. This review describes the physiology of fracture healing, with a focus on aspects of natural repair that may be pharmacologically augmented to prevent or treat delayed or nonunion fractures (collectively referred to as DNFs). The agents covered in this review include recombinant BMPs, PTH/PTHrP receptor agonists, activators of Wnt/β-catenin signaling, and recombinant FGF-2. Agents from these therapeutic classes have undergone extensive preclinical testing and progressed to clinical fracture healing trials. Each can promote bone formation, which is important for the stability of bridged calluses, and some but not all can also promote cartilage formation, which may be critical for the initial bridging and subsequent stabilization of fractures. Appropriately timed stimulation of chondrogenesis and osteogenesis in the fracture callus may be a more effective approach for preventing or treating DNFs compared with stimulation of osteogenesis alone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:213-223, 2017.
| S-EPMC6120140 | biostudies-literature