Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Giulia Montagna, Giuseppe Pani, Dani Flinkman, Francesco Cristofaro, Barbara Pascucci, Luca Massimino, Luigi Antonio Lamparelli, Lorenzo Fassina, Peter James, Eleanor Coffey, Giuseppina Rea, Livia Visai, Angela Maria Rizzo

Research output: Contribution to journalArticlepeer-review


Microgravity-induced bone loss is a major concern for space travelers. Ground-based microgravity simulators are crucial to study the effect of microgravity exposure on biological systems and to address the limitations posed by restricted access to real space. In this work, for the first time, we adopt a multidisciplinary approach to characterize the morphological, biochemical, and molecular changes underlying the response of human bone marrow stromal cells to long-term simulated microgravity exposure during osteogenic differentiation. Our results show that osteogenic differentiation is reduced while energy metabolism is promoted. We found novel proteins were dysregulated under simulated microgravity, including CSC1-like protein, involved in the mechanotransduction of pressure signals, and PTPN11, SLC44A1 and MME which are involved in osteoblast differentiation pathways and which may become the focus of future translational projects. The investigation of cell proteome highlighted how simulated microgravity affects a relatively low number of proteins compared to time and/or osteogenic factors and has allowed us to reconstruct a hypothetical pipeline for cell response to simulated microgravity. Further investigation focused on the application of nanomaterials may help to increase understanding of how to treat or minimize the effects of microgravity.

Original languageEnglish
Article number536
JournalCellular and Molecular Life Sciences
Issue number10
Publication statusPublished - 2022 Oct

Bibliographical note

Funding Information:
The authors would like to thank all the components of the Proteomics Core at the Turku Bioscience Centre for their guidance and support. The authors would like to acknowledge the Italian Space Agency Team.

Funding Information:
Open access funding provided by Università degli Studi di Pavia within the CRUI-CARE Agreement. This work was supported by a grant from the Italian Space Agency Project DC-MIC-2012-024, contract N. 2013-060-I.O to L.V., G.R., and A.M.R. This research was also supported by a grant of the Italian Ministry of Education, University and Research (MIUR) to the Department of Molecular Medicine of the University of Pavia under the initiative “Dipartimenti di Eccellenza (2018–2022)” and Projects of High Relevance, Bilateral project Italy-Sweden, Ministry of Foreign Affairs and International Cooperation (MAECI), and Ministry of Education, University and Research (MIUR) (2018–2020) titled “Effect of hydRoxyapatitE nanoPArticles on bone regeneration In simulated micRogravity (REPAIR)” to LV.

Publisher Copyright:
© 2022, The Author(s).

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology

Free keywords

  • Bioimaging
  • Bone extracellular matrix
  • Cytoskeleton
  • Data-independent acquisition
  • Human primary cells
  • Osteogenic biomarkers
  • Proteomics
  • Secondary osteoporosis
  • Simulated microgravity


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