Aged skeletal stem cells during fracture healing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA700970 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13666749_1.fastq.gz | Fastqsanger.gz | |||
| SRR13666749_2.fastq.gz | Fastqsanger.gz | |||
| SRR13666750_1.fastq.gz | Fastqsanger.gz | |||
| SRR13666750_2.fastq.gz | Fastqsanger.gz | |||
| SRR13666751_1.fastq.gz | Fastqsanger.gz |
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Project description:Skeletal aging and disease are associated with a misbalance in the opposing actions of osteoblasts and osteoclasts that are responsible for maintaining the integrity of bone tissues. Here, we show through detailed functional and single-cell genomic studies that intrinsic aging of bona fide mouse skeletal stem cells (SSCs) alters bone marrow niche signaling and skews bone and blood lineage differentiation leading to fragile bones that regenerate poorly. Aged SSCs have diminished bone and cartilage forming potential but produce higher frequencies of stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell transcriptomic studies reveal a distinct population of SSCs in aged mice that gradually outcompete their younger counterparts in the bone marrow niche. While systemic exposure to a youthful circulation through heterochronic parabiosis reduced local expression of inflammatory cytokines, it did not reverse the diminished osteochondrogenic activity of aged SSCs and was insufficient to improve bone mass and skeletal-healing parameters in aged mice. Hematopoietic reconstitution of aged mice with young hematopoietic stem cells (HSC) also did not improve bone integrity and repair. We find that deficient bone regeneration in aged mice could only be reversed by the local application of a combinatorial treatment that re-activates aged SSCs and simultaneously abates crosstalk to hematopoietic cells favoring an inflammatory milieu. This treatment expanded aged SSC pools, reduced osteoclast activity, and enhanced bone healing to youthful levels. Our findings provide mechanistic insight into the complex, multifactorial mechanisms underlying skeletal aging and offer new prospects for rejuvenating the aged skeletal system.
2021-06-11 | GSE166441 | GEO
Project description:Despite its regenerative capacity, the healing potential of bone tissue declines with aging. With the increase in global aging population, bone fractures pose a tremendous burden to the healthcare system. Therapeutic interventions that circumvent age-associated impairments and promote bone tissue regeneration are attractive options for geriatric fracture repair. We and others have demonstrated the role of extracellular adenosine in bone homeostasis and regeneration. Herein, we examined the changes in extracellular adenosine with aging and the potential of local delivery of adenosine to promote fracture healing using aged mice as a model system. Extracellular adenosine level was significantly lower in aged bone tissue compared to those from young mice. Concomitantly, the ecto-5′-nucleotidase CD73 expression was also found to be lower in the aged bone tissue. Local delivery of adenosine using injectable, in situ curing microgel delivery units yielded a pro-regenerative environment and promoted fracture healing in aged mice. This study offers new insights into age-related physiological changes in adenosine levels and demonstrates the therapeutic potential of adenosine supplementation to circumvent the compromised healing of geriatric fractures.
2025-04-16 | GSE272155 | GEO
Project description:Enabling adenosine signaling to promote aged 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 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:A study of rat femoral fracture healing in young (6 weeks old at fracture), adult (26 weeks old at fracture), and old (52 weeks old at fracture) rats. Samples were collected at time of surgery (intact controls) and at 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after fracture. Samples were the mid third of the femoral length including the external callus, cortical bone and marrow elements. Fracture was stabilized with an intramedullary rod prior to fracture with a Bonnarens and Einhorn device.
2007-11-03 | E-GEOD-1371 | biostudies-arrayexpress
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
Project description:Bone fracture healing shows approximately 10-15% non-unions, although theoretically it has the potential of scarless regeneration. With regards to our aging society, a better understanding of the healing process is needed to allow for more sophisticated treatment options. Particular the early phase, which is a high complex and dynamic process in regards to nutrient and engery requirements. Here we investigate the proteomic (and metabolic) characteristics of the local microenvironment from successful (in young female Sprague-Dawley rats) and biologically compromised (in aged female rats with a minimum litter of three)bone reneration at day 3, 7 and 14 after osteotomy.
2023-05-10 | PXD020085 | Pride
Project description:Skeletal aging and disease are associated with a misbalance in the opposing actions of osteoblasts and osteoclasts that are responsible for maintaining the integrity of bone tissues. Here, we show through detailed functional and single-cell genomic studies that intrinsic aging of bona fide mouse skeletal stem cells (SSCs) alters bone marrow niche signaling and skews bone and blood lineage differentiation leading to fragile bones that regenerate poorly. Aged SSCs have diminished bone and cartilage forming potential but produce higher frequencies of stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell transcriptomic studies reveal a distinct population of SSCs in aged mice that gradually outcompete their younger counterparts in the bone marrow niche. While systemic exposure to a youthful circulation through heterochronic parabiosis reduced local expression of inflammatory cytokines, it did not reverse the diminished osteochondrogenic activity of aged SSCs and was insufficient to improve bone mass and skeletal-healing parameters in aged mice. Hematopoietic reconstitution of aged mice with young hematopoietic stem cells (HSC) also did not improve bone integrity and repair. We find that deficient bone regeneration in aged mice could only be reversed by the local application of a combinatorial treatment that re-activates aged SSCs and simultaneously abates crosstalk to hematopoietic cells favoring an inflammatory milieu. This treatment expanded aged SSC pools, reduced osteoclast activity, and enhanced bone healing to youthful levels. Our findings provide mechanistic insight into the complex, multifactorial mechanisms underlying skeletal aging and offer new prospects for rejuvenating the aged skeletal system.
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