Advanced search
1 file | 1.01 MB

Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis

(2017) EPIGENETICS. 12(2). p.113-122
Author
Organization
Abstract
Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation.
Keywords
Epigenetics, osteoarthritis, osteoporosis, stem cells, transcription factors, DNA METHYLATION, SUBCHONDRAL BONE, OSTEOPOROSIS, BMP-2, STIMULATION, MECHANISMS, CARTILAGE, SKELETAL, REGIONS, LINEAGE

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.01 MB

Citation

Please use this url to cite or link to this publication:

Chicago
del Real, Alvaro, Flor M Pérez-Campo, Agustín F Fernández, Carolina Sañudo, Carmen G Ibarbia, María I Pérez-Núñez, Wim Van Criekinge, et al. 2017. “Differential Analysis of Genome-wide Methylation and Gene Expression in Mesenchymal Stem Cells of Patients with Fractures and Osteoarthritis.” Epigenetics 12 (2): 113–122.
APA
del Real, A., Pérez-Campo, F. M., Fernández, A. F., Sañudo, C., Ibarbia, C. G., Pérez-Núñez, M. I., Van Criekinge, W., et al. (2017). Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis. EPIGENETICS, 12(2), 113–122.
Vancouver
1.
del Real A, Pérez-Campo FM, Fernández AF, Sañudo C, Ibarbia CG, Pérez-Núñez MI, et al. Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis. EPIGENETICS. 2017;12(2):113–22.
MLA
del Real, Alvaro, Flor M Pérez-Campo, Agustín F Fernández, et al. “Differential Analysis of Genome-wide Methylation and Gene Expression in Mesenchymal Stem Cells of Patients with Fractures and Osteoarthritis.” EPIGENETICS 12.2 (2017): 113–122. Print.
@article{8553458,
  abstract     = {Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation.},
  author       = {del Real, Alvaro and P{\'e}rez-Campo, Flor M and Fern{\'a}ndez, Agust{\'i}n F and Sa{\~n}udo, Carolina and Ibarbia, Carmen G and P{\'e}rez-N{\'u}{\~n}ez, Mar{\'i}a I and Van Criekinge, Wim and Braspenning, Maarten and Alonso, Mar{\'i}a A and Fraga, Mario F and Riancho, Jose A},
  issn         = {1559-2294},
  journal      = {EPIGENETICS},
  keyword      = {Epigenetics,osteoarthritis,osteoporosis,stem cells,transcription factors,DNA METHYLATION,SUBCHONDRAL BONE,OSTEOPOROSIS,BMP-2,STIMULATION,MECHANISMS,CARTILAGE,SKELETAL,REGIONS,LINEAGE},
  language     = {eng},
  number       = {2},
  pages        = {113--122},
  title        = {Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis},
  url          = {http://dx.doi.org/10.1080/15592294.2016.1271854},
  volume       = {12},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: