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.
Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria
Fuente: Epigenetics. 2017 Feb;12(2):113-122
Editorial: Taylor & Francis
Fecha de publicación: 01/02/2017
Nº de páginas: 10
Tipo de publicación: Artículo de Revista
DOI: 10.1080/15592294.2016.1271854
ISSN: 1559-2294,1559-2308