Human osteogenic differentiation in Space: proteomic and epigenetic clues to better understand osteoporosis

Alessandra Gambacurta, Giulia Merlini, Cristina Ruggiero, Giacomo Diedenhofen, Natalia Battista, Monica Bari, Michele Balsamo, Sara Piccirillo, Giovanni Valentini, Gabriele Mascetti, Mauro Maccarrone

Research output: Contribution to journalArticlepeer-review

Abstract

In the frame of the VITA mission of the Italian Space Agency (ASI), we addressed the problem of Space osteoporosis by using human blood-derived stem cells (BDSCs) as a suitable osteogenic differentiation model. In particular, we investigated proteomic and epigenetic changes in BDSCs during osteoblastic differentiation induced by rapamycin under microgravity conditions. A decrease in the expression of 4 embryonic markers (Sox2, Oct3/4, Nanog and E-cadherin) was found to occur to a larger extent on board the ISS than on Earth, along with an earlier activation of the differentiation process towards the osteogenic lineage. The changes in the expression of 4 transcription factors (Otx2, Snail, GATA4 and Sox17) engaged in osteogenesis supported these findings. We then ascertained whether osteogenic differentiation of BDSCs could depend on epigenetic regulation, and interrogated changes of histone H3 that is crucial in this type of gene control. Indeed, we found that H3K4me3, H3K27me2/3, H3K79me2/3 and H3K9me2/3 residues are engaged in cellular reprogramming that drives gene expression. Overall, we suggest that rapamycin induces transcriptional activation of BDSCs towards osteogenic differentiation, through increased GATA4 and Sox17 that modulate downstream transcription factors (like Runx2), critical for bone formation. Additional studies are warranted to ascertain the possible exploitation of these data to identify new biomarkers and therapeutic targets to treat osteoporosis, not only in Space but also on Earth.

Original languageEnglish
Number of pages1
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Jun 6 2019

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Human osteogenic differentiation in Space: proteomic and epigenetic clues to better understand osteoporosis'. Together they form a unique fingerprint.

Cite this