title: Comparative proteomic profiling of human osteoblast-derived extracellular matrices identifies proteins involved in mesenchymal stromal cell osteogenic differentiation and mineralization.
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.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marta
authors.identifier: http://orcid.org/0000-0002-3723-5538
authors.initials: M
authors.lastname: Baroncelli
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bram C
authors.initials: BC
authors.lastname: van der Eerden
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Yik-Yang
authors.initials: YY
authors.lastname: Kan
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Rodrigo D
authors.initials: RD
authors.lastname: Alves
authors.affiliation: Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeroen A
authors.initials: JA
authors.lastname: Demmers
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van de Peppel
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Johannes P
authors.initials: JP
authors.lastname: van Leeuwen
mesh_terms: D028341:Activins / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D012269:Ribosomal Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D016326:Extracellular Matrix Proteins; D012269:Ribosomal Proteins; C422405:activin A; D028341:Activins
keywords: Activin-A; bone regeneration; extracellular matrix; mesenchymal stromal cells