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

Corina-Adriana Ghebes; Jéré van Lente; Janine Nicole Post; Daniel B F Saris; Hugo Fernandes

doi:10.1177/1087057116669346

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

Corina-Adriana Ghebes, Jéré van Lente, Janine Nicole Post, Daniel B F Saris, Hugo Fernandes

Regenerative Medicine and Stem Cells

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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.

Original language	English
Pages (from-to)	40-50
Number of pages	11
Journal	Journal of biomolecular screening
Volume	22
Issue number	1
Early online date	14 Sept 2016
DOIs	https://doi.org/10.1177/1087057116669346
Publication status	Published - Jan 2017

Keywords

MP-2 signaling
TGF-β1 signaling
small-molecule discovery
tendon/ligament
BMP-2 signaling

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10.1177/1087057116669346Licence: CC BY-NC-ND

1-s2.0-S2472555222069349-mainFinal published version, 3.41 MBLicence: CC BY-NC-ND

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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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AU - Saris, Daniel B F

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

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