Towards targeting overactive BMP signaling in Fibrodysplasia Ossificans Progressiva


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


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.

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


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