Mesenchymal cell-derived septoclasts resorb cartilage during endochondral ossification and fracture healing
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ABSTRACT:
PROVIDER: PRJNA645569 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal cell-derived septoclasts resorb cartilage during endochondral ossification and fracture healing
2021-12-11 | GSE154076 | GEO
Project description:Mesenchymal cell-derived septoclasts resorb cartilage during endochondral ossification and fracture healing
| PRJNA645073 | ENA
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: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:For scRNA-seq of fracture bone , 14 days post-fracture (PFD14) femur and control bones were harvested, cleaned surrounding tissue and the nail insert was removed from fracture bone. Control and PFD14 bone single cell suspension and non-hematopoietic stromal cells were prepared for scRNA-seq .
2021-12-10 | GSE154247 | GEO
Project description:Transcriptional profiling of intramembranous and endochondral ossification after fracture in mice
| PRJNA640062 | ENA
Project description:Maturation of the 3¢ end of almost all eukaryotic messenger RNAs (mRNAs) requires cleavage and polyadenylation. Most mammalian mRNAs are polyadenylated at different sites within the last exon, generating alternative polyadenylation (APA) isoforms that have the same coding region but distinct 3¢ untranslated regions (UTRs). The 3¢UTR contains motifs that regulate mRNA metabolism; thus, changing the 3¢UTR length via APA can significantly impact gene expression. Endochondral ossification is a central process in bone healing, and the impact of APA on gene expression during this process is unknown. Here, we report widespread utilization of APA that impacts multiple pathways with established roles in bone healing. Importantly, progression of endochondral ossification is typified by global 3¢UTR shortening that is coupled with an increased abundance of shortened transcripts as compared to all other transcripts, underscoring the role of APA in promoting gene expression during endochondral bone formation. Our mechanistic studies of genes that undergo APA in the fracture callus uncover an intricate regulatory network in which APA boosts the expression of collagen, type I, alpha 1 (Col1a1) and Col1a2 genes, which encode the 2 subunits of the abundantly expressed protein collagen 1. APA does so via shortening the 3¢UTRs of Col1a1 and Col1a2 mRNAs, which removes the binding sites of miR-29a-3p that otherwise potently triggered the degradation of both transcripts. Taken together, our study takes the lead in characterizing crucial roles of APA in tailoring the 3¢UTR landscape and regulating gene expression during fracture healing.
2023-01-11 | GSE205053 | GEO
Project description:β-NGF promotes cartilage to bone conversion, accelerating endochondral fracture repair
| PRJNA631146 | ENA
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:Extracellular vesicle cargo proteins shed new light on bone formation healing: Extracellular vesicle cargo proteins shed new light on bone formation
2022-04-01 | PXD030478 | Pride