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

SLAS Discov. 2017 Jan;22(1):40-50. doi: 10.1177/1087057116669346. Epub 2016 Sep 27.

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.

Keywords: BMP-2 signaling; TGF-β1 signaling; small-molecule discovery; tendon/ligament.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / metabolism*
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Collagen / metabolism
  • Gene Expression Regulation / drug effects
  • Genes, Reporter
  • High-Throughput Screening Assays / methods*
  • Humans
  • Mice
  • Mink
  • Protein Transport / drug effects
  • Reproducibility of Results
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Small Molecule Libraries / pharmacology*
  • Tendons / cytology
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Smad Proteins
  • Small Molecule Libraries
  • Transforming Growth Factor beta1
  • Collagen
  • Alkaline Phosphatase