title: High-Throughput Screening Assay Identifies Small Molecules Capable of Modulating the BMP-2 and TGF-β1 Signaling Pathway.
abstract: Modulating the bone morphogenetic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) signaling pathways is essential during tendon/ligament (T/L) healing. Unfortunately, growth factor delivery in situ is far from trivial and, in many cases, the necessary growth factors are not approved for clinical use. Here we used a BMP-2 and a TGF-β1 reporter cell line to screen a library of 1280 Food and Drug Administration-approved small molecules and identify modulators of both signaling pathways. We identified four compounds capable of modulating BMP and TGF signaling on primary human tendon-derived cells (huTCs) and describe their effects on proliferation and differentiation of these cells.
authors.affiliation: 1 MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Corina-Adriana
authors.initials: CA
authors.lastname: Ghebes
authors.affiliation: 1 MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Jéré
authors.initials: J
authors.lastname: van Lente
authors.affiliation: 1 MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Janine Nicole
authors.initials: JN
authors.lastname: Post
authors.affiliation: 1 MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|2 Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.affiliation: 1 MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|3 Center for Neuroscience and Cell Biology (CNC), Stem Cells and Drug Screening Lab, University of Coimbra, Coimbra, Portugal.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandes
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D051379:Mice; D008907:Mink; D021381:Protein Transport / Q000187:drug effects; D015203:Reproducibility of Results; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013710:Tendons / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D051785:Smad Proteins; D054852:Small Molecule Libraries; D053773:Transforming Growth Factor beta1; D003094:Collagen; D000469:Alkaline Phosphatase
keywords: BMP-2 signaling; TGF-β1 signaling; small-molecule discovery; tendon/ligament