Old Mice Have Less Transcriptional Activation But Similar Periosteal Cell Proliferation Compared to Young-Adult Mice in Response to in vivo Mechanical Loading
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ABSTRACT:
PROVIDER: PRJNA662558 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12616600.fastq.gz | Fastqsanger.gz | |||
| SRR12616601.fastq.gz | Fastqsanger.gz | |||
| SRR12616602.fastq.gz | Fastqsanger.gz | |||
| SRR12616603.fastq.gz | Fastqsanger.gz | |||
| SRR12616604.fastq.gz | Fastqsanger.gz |
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Project description:Mechanical loading is a potent strategy to induce bone formation, but with aging, the bone formation response to the same mechanical stimulus diminishes. Our main objectives were to (i) discover the potential transcriptional differences and (ii) compare the periosteal cell proliferation between tibias of young-adult and old mice in response to strain-matched mechanical loading. First, to discover potential age-related transcriptional differences, we performed RNA sequencing (RNA-seq) to compare the loading responses between tibias of young-adult (5-month) and old (22-month) C57BL/6N female mice following 1, 3, or 5 days of axial loading (loaded versus non-loaded). Compared to young-adult mice, old mice had less transcriptional activation following loading at each time point, as measured by the number of differentially expressed genes (DEGs) and the fold-changes of the DEGs. Old mice engaged fewer pathways and gene ontology (GO) processes, showing less activation of processes related to proliferation and differentiation. In tibias of young-adult mice, we observed prominent Wnt signaling, extracellular matrix (ECM), and neuronal responses, which were diminished with aging. Additionally, we identified several targets that may be effective in restoring the mechanoresponsiveness of aged bone, including nerve growth factor (NGF), Notum, prostaglandin signaling, Nell-1, and the AP-1 family. Second, to directly test the extent to which periosteal cell proliferation was diminished in old mice, we used bromodeoxyuridine (BrdU) in a separate cohort of mice to label cells that divided during the 5-day loading interval. Young-adult and old mice had an average of 15.5 and 16.7 BrdU+ surface cells/mm, respectively, suggesting that impaired proliferation in the first 5 days of loading does not explain the diminished bone formation response with aging. We conclude that old mice have diminished transcriptional activation following mechanical loading, but periosteal proliferation in the first 5 days of loading does not differ between tibias of young-adult and old mice.
2020-09-10 | GSE157719 | GEO
Project description:Mechanical loading is a potent strategy to induce bone formation, but with aging, the bone formation response to the same mechanical stimulus diminishes. Our main objectives were to (i) discover the potential transcriptional differences and (ii) compare the periosteal cell proliferation between tibias of young-adult and old mice in response to strain-matched mechanical loading. First, to discover potential age-related transcriptional differences, we performed RNA sequencing (RNA-seq) to compare the loading responses between tibias of young-adult (5-month) and old (22-month) C57BL/6N female mice following 1, 3, or 5 days of axial loading (loaded versus non-loaded). Compared to young-adult mice, old mice had less transcriptional activation following loading at each time point, as measured by the number of differentially expressed genes (DEGs) and the fold-changes of the DEGs. Old mice engaged fewer pathways and gene ontology (GO) processes, showing less activation of processes related to proliferation and differentiation. In tibias of young-adult mice, we observed prominent Wnt signaling, extracellular matrix (ECM), and neuronal responses, which were diminished with aging. Additionally, we identified several targets that may be effective in restoring the mechanoresponsiveness of aged bone, including nerve growth factor (NGF), Notum, prostaglandin signaling, Nell-1, and the AP-1 family. Second, to directly test the extent to which periosteal cell proliferation was diminished in old mice, we used bromodeoxyuridine (BrdU) in a separate cohort of mice to label cells that divided during the 5-day loading interval. Young-adult and old mice had an average of 15.5 and 16.7 BrdU+ surface cells/mm, respectively, suggesting that impaired proliferation in the first 5 days of loading does not explain the diminished bone formation response with aging. We conclude that old mice have diminished transcriptional activation following mechanical loading, but periosteal proliferation in the first 5 days of loading does not differ between tibias of young-adult and old mice. © 2020 American Society for Bone and Mineral Research.
| S-EPMC7486279 | biostudies-literature
Project description:To gain insights into the role of Prmt5 in osteoclasts and periosteal stem cells , we performed RNA sequencing (RNA-seq) on osteoclasts and periosteal stem cells from control and Prmt5 f/d Ctsk-Cre mice
2022-05-07 | GSE146872 | GEO
Project description:BackgroundThe adaptive nature of bone formation under mechanical loading is well known; however, the molecular and cellular mechanisms in vivo of mechanical loading in bone formation are not fully understood. To investigate both mechanisms at the early response against mechanotransduction in vivo, we employed a noninvasive 3-point bone bending method for mouse tibiae. It is important to investigate periosteal woven bone formation to elucidate the adaptive nature against mechanical stress. We hypothesize that cell morphological alteration at the early stage of mechanical loading is essential for bone formation in vivo.Principal findingsWe found the significant bone formation on the bone surface subjected to change of the stress toward compression by this method. The histological analysis revealed the proliferation of periosteal cells, and we successively observed the appearance of ALP-positive osteoblasts and increase of mature BMP-2, resulting in woven bone formation in the hypertrophic area. To investigate the mechanism underlying the response to mechanical loading at the molecular level, we established an in-situ immunofluorescence imaging method to visualize molecules in these periosteal cells, and with it examined their cytoskeletal actin and nuclei and the extracellular matrix proteins produced by them. The results demonstrated that the actin cytoskeleton of the periosteal cells was disorganized, and the shapes of their nuclei were drastically changed, under the mechanical loading. Moreover, the disorganized actin cytoskeleton was reorganized after release from the load. Further, inhibition of onset of the actin remodeling blocked the proliferation of the periosteal cells.ConclusionsThese results suggest that the structural change in cell shape via disorganization and remodeling of the actin cytoskeleton played an important role in the mechanical loading-dependent proliferation of cells in the periosteum during bone formation.
| S-EPMC3173483 | biostudies-literature
Project description:The aim of the current study was to quantify the local effect of mechanical loading on cortical bone formation response at the periosteal surface using previously obtained μCT data from a mouse tibia mechanical loading study. A novel image analysis algorithm was developed to quantify local cortical thickness changes (ΔCt.Th) along the periosteal surface due to different peak loads (0N ≤ F ≤ 12N) applied to right-neurectomised mature female C57BL/6 mice. Furthermore, beam analysis was performed to analyse the local strain distribution including regions of tensile, compressive, and low strain magnitudes. Student's paired t-test showed that ΔCt.Th in the proximal (25%), proximal/middle (37%), and middle (50%) cross-sections (along the z-axis of tibia) is strongly associated with the peak applied loads. These changes are significant in a majority of periosteal positions, in particular those experiencing high compressive or tensile strains. No association between F and ΔCt.Th was found in regions around the neutral axis. For the most distal cross-section (75%), the association of loading magnitude and ΔCt.Th was not as pronounced as the more proximal cross-sections. Also, bone formation responses along the periosteum did not occur in regions of highest compressive and tensile strains predicted by beam theory. This could be due to complex experimental loading conditions which were not explicitly accounted for in the mechanical analysis. Our results show that the bone formation response depends on the load magnitude and the periosteal position. Bone resorption due to the neurectomy of the loaded tibia occurs throughout the entire cross-sectional region for all investigated cortical sections 25, 37, 50, and 75%. For peak applied loads higher than 4 N, compressive and tensile regions show bone formation; however, regions around the neutral axis show constant resorption. The 50% cross-section showed the most regular ΔCt.Th response with increased loading when compared to 25 and 37% cross-sections. Relative thickness gains of approximately 70, 60, and 55% were observed for F = 12 N in the 25, 37, and 50% cross-sections. ΔCt.Th at selected points of the periosteum follow a linear response with increased peak load; no lazy zone was observed at these positions.
| S-EPMC8249932 | biostudies-literature
Project description:The periosteum contains cells which function as a reservoir of stem cells and progenitors and contribute to cortical expansion during growth, cortical bone homeostasis and repair. However, the local or paracrine factors that govern stem cell renewal and differentiation within the periosteal niche remains elusive. Cathepsin K (Ctsk) together with additional cell surface markers marks a subset of stem cells in the periosteum (PSC) which possess self-renewal ability and inducible multipotency. These PSCs produce osteoblasts mediating periosteal bone formation and fracture repair. Sfrp4 is expressed in periosteal Ctsk-lineage cells and using CtskCre mice that are either wild type or Sfrp4-/-, we report here that Sfrp4 deletion decreases the pool of PSCs, impairs their self-renewal, their ability to give rise to their derivatives and their clonal multipotency for differentiation into osteoblasts and chondrocytes in vitro and formation of bone organoids in vivo. Bulk RNA sequencing analysis in Ctsk-lineage PSCs demonstrated that Sfrp4 deletion leads to downregulation of signaling pathways associated with skeletal development, positive regulation of bone mineralization and wound healing. Sfrp4 deletion hampers the Ctsk-lineage PSC response and recruitment after bone injury and leads to an impaired periosteal response. Periosteal Ctsk-lineage cells respond to PTH(1-34) treatment with an increase in the % of PSCs, a response not seen in the absence of Sfrp4. Importantly, bone histomorphometry analysis showed that in the absence of Sfrp4, PTH(1-34)-dependent increase in cortical thickness, periosteal bone formation is markedly impaired.
2024-08-13 | GSE236686 | GEO
Project description:Bone regeneration is a highly efficient process allowing scarless healing after injury. The periosteum, the outer layer of bones, is a critical source of skeletal stem/progenitor cells (SSPCs), as well as immune, endothelial and neural cells during bone repair. In our study, we generated a single-nuclei atlas of the murine periosteal response to bone fracture. We generated single nuclei datasets from uninjured periosteum and from injured periosteum and hematoma/fracture callus at days 5 and 7 post-injury from wild-type mice.
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Project description:Genetic comparison between periosteal skeletal stem cells and bone marrow skeletal stem cells in mice
2017-12-08 | GSE107798 | GEO
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