Comparative proteomic profiling of human osteoblast-derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization

Marta Baroncelli, Bram C. van der Eerden, Yik-Yang Kan, Rodrigo D. Alves, Jeroen A. Demmers, Jeroen van de Peppel, Johannes P. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The extracellular matrix (ECM) is a dynamic component of tissue architecture that physically supports cells and actively influences their behavior. In the context of bone regeneration, cell-secreted ECMs have become of interest as they reproduce tissue-architecture and modulate the promising properties of mesenchymal stem cells (MSCs). We have previously created an in vitro model of human osteoblast-derived devitalized ECM that was osteopromotive for MSCs. The aim of this study was to identify ECM regulatory proteins able to modulate MSC differentiation to broaden the spectrum of MSC clinical applications. To this end, we created two additional models of devitalized ECMs with different mineralization phenotypes. Our results showed that the ECM derived from osteoblast-differentiated MSCs had increased osteogenic potential compared to ECM derived from undifferentiated MSCs and non-ECM cultures. Proteomic analysis revealed that structural ECM proteins and ribosomal proteins were upregulated in the ECM from undifferentiated MSCs. A similar response profile was obtained by treating osteoblast-differentiating MSCs with Activin-A. Extracellular proteins were upregulated in Activin-A ECM, whereas mitochondrial and membrane proteins were downregulated. In summary, this study illustrates that the composition of different MSC-secreted ECMs is important to regulate the osteogenic differentiation of MSCs. These models of devitalized ECMs could be used to modulate MSC properties to regulate bone quality.
Original languageEnglish
Pages (from-to)387-395
Number of pages9
JournalJournal of Cellular Physiology
Volume233
Issue number1
DOIs
Publication statusPublished - Jan 2018

Bibliographical note

Funding information:
Netherlands Institute for Regenerative
Medicine, Grant number: FES0908

Research programs

  • EMC MGC-02-02-01
  • EMC MM-01-39-02

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