Towards targeting overactive BMP signaling in Fibrodysplasia Ossificans Progressiva

  • Jente van Staalduinen Leiden University
  • Gonzalo Sánchez-Duffhues Leiden University
  • Peter ten Dijke Leiden University

Abstract

Fibrodysplasia Ossificans Progressiva (FOP) is a rare monogenetic disorder in which patients develop heterotopic ossification (HO). A heterozygous mutation in BMP type I receptor ALK2 results in hyper-sensitized BMP signaling. The aim of this study is to identify small molecules which can selectively inhibit this overactive BMP pathway. Thirteen FDA-approved small molecules were tested on their effect on BMP6-induced target gene expression, alkaline phosphatase activity and mineralization in KS483 cells. We identified cryptotanshinone as a small molecule able to inhibit BMP signaling. In conclusion, cryptotanshinone could be a novel small molecule inhibitor of the overactive BMP signaling pathway in FOP.

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Author Biographies

Jente van Staalduinen, Leiden University
Leiden University Medical Center
Gonzalo Sánchez-Duffhues, Leiden University
Leiden University Medical Center
Peter ten Dijke, Leiden University
Leiden University Medical Center
How to Cite
VAN STAALDUINEN, Jente; SÁNCHEZ-DUFFHUES, Gonzalo; TEN DIJKE, Peter. Towards targeting overactive BMP signaling in Fibrodysplasia Ossificans Progressiva. Student Undergraduate Research E-journal!, [S.l.], v. 1, nov. 2015. ISSN 2468-0443. Available at: <https://journals.library.tudelft.nl/index.php/sure/article/view/1041>. Date accessed: 18 jan. 2019.
Published
2015-11-20