High-Throughput Screening Assay Identifies Small Molecules Capable of Modulating the BMP-2 and TGF-β1 Signaling Pathway

Corina-Adriana Ghebes, Jeré van Lente, Janine Nicole Post, Daniël B.F. Saris, Hugo Fernandes

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalSLAS DISCOVERY: Advancing Life Sciences R&D
Volume22
Issue number1
Early online date14 Sep 2016
DOIs
Publication statusPublished - 1 Jan 2017

Fingerprint

High-Throughput Screening Assays
Bone Morphogenetic Protein 2
Assays
Intercellular Signaling Peptides and Proteins
Screening
Throughput
Molecules
Growth
Cells
Ligaments
Tendons
Libraries
Cell Differentiation
Cell Proliferation
Cell Line
Food
Modulators
Pharmaceutical Preparations

Keywords

  • BMP-2 signaling
  • Small-molecule discovery
  • Tendon/ligament
  • TGF-β1 signaling
  • IR-102828
  • METIS-320218

Cite this

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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.",
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High-Throughput Screening Assay Identifies Small Molecules Capable of Modulating the BMP-2 and TGF-β1 Signaling Pathway. / Ghebes, Corina-Adriana; van Lente, Jeré; Post, Janine Nicole; Saris, Daniël B.F.; Fernandes, Hugo.

In: SLAS DISCOVERY: Advancing Life Sciences R&D, Vol. 22, No. 1, 01.01.2017, p. 40-50.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Ghebes, Corina-Adriana

AU - van Lente, Jeré

AU - Post, Janine Nicole

AU - Saris, Daniël B.F.

AU - Fernandes, Hugo

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AB - 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.

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