Impaired bone fracture healing in type 2 diabetes is caused by defective functions of skeletal progenitor cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA748427 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15202775_1.fastq.gz | Fastqsanger.gz | |||
| SRR15202775_2.fastq.gz | Fastqsanger.gz | |||
| SRR15202776_1.fastq.gz | Fastqsanger.gz | |||
| SRR15202776_2.fastq.gz | Fastqsanger.gz | |||
| SRR15202777_1.fastq.gz | Fastqsanger.gz |
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Project description:Rejuvenating Age-impaired Fracture Healing
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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:The mechanisms of obesity and type 2 diabetes (T2D)-associated impaired fracture healing are poorly studied. In a murine model of T2D reflecting both hyperinsulinemia induced by high fat diet (HFD) and insulinopenia induced by treatment with streptozotocin (STZ), we examined bone healing in a tibia cortical bone defect. A delayed bone healing was observed during hyperinsulinemia as newly formed bone was reduced by – 28.4±7.7% and was associated with accumulation of marrow adipocytes at the defect site +124.06±38.71%, and increased density of SCA1+ (+74.99± 29.19%) but not Runx2+osteoprogenitor cells. We also observed increased in reactive oxygen species production (+101.82± 33.05%), senescence gene signature (≈106.66± 34.03%) and LAMIN B1- senescent cell density (+225.18± 43.15%), suggesting accelerated senescence phenotype. During insulinopenia, a more pronounced delayed bone healing was observed with decreased newly formed bone to -34.9± 6.2% which was inversely correlated with glucose levels (R2=0.48, p<0.004) and callus adipose tissue area (R2=0.3711, p<0.01). Finally, to investigate the relevance to human physiology, we observed that sera from obese and T2D patients exerted inhibitory effects on osteoblastic and enhanced adipocyte differentiation of human bone marrow stromal stem cells. Our data demonstrate that T2D exerts negative effects on bone healing through inhibition of osteoblast differentiation of skeletal stem cells and induction of accelerated bone senescence and that the hyperglycaemia per se and not just insulin levels is detrimental for bone healing.
2021-10-01 | GSE180504 | 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 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: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.
2013-10-25 | GSE51686 | GEO
Project description:Phosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized. We used data from microarrays to (1) determine the effects of phosphate restriction on the biologic functions identified from the gene expression in fracture calluses; and (2) examine whether there are genetic differences within the primary biologic functions.
2018-12-25 | GSE99580 | GEO
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:Sprague-Dawley rats were placed on an ethanol-containing or pair-fed Lieber and DeCarli diets for 4 wks prior to surgical fracture. Following insertion of a medullary pin, a closed mid-diaphyseal fracture was induced using a Bonnarens and Einhorn fracture device. At 3 days post-fracture, the region of the fracture calluses were harvested from the right hind-limb. RNA was extracted and microarray analysis was conducted against the entire rat genome to study the effects of alcohol-consumption on the fracture healing. The experiments were on four rat subjects, i.e., pair-fed rats with subsequent surgical fracture or no surgical fracture, and alcohol-fed rats with subsequent surgical fracture or no surgical fracture. Each rat subject described above has three replicates so 6 kinds of pairing can be made and each pairing has a dye-swap replicate (thus, a total 12 array experiments). The focus of this study is on the pair-fed fracture subject vs. alcohol-fed fracture subject.
2011-05-01 | E-GEOD-16003 | biostudies-arrayexpress