Mast cell inhibition as a therapeutic approach in fibrodysplasia ossificans progressiva (FOP)

Tracy A. Brennan, Carter M. Lindborg, Christian R. Bergbauer, Haitao Wang, Frederick S. Kaplan, Robert Pignolo

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: Episodic flare-ups of fibrodysplasia ossificans progressiva (FOP) are characterized clinically by severe, often posttraumatic, connective tissue swelling and intramuscular edema, followed histologically by an intense and highly angiogenic fibroproliferative reaction. This early inflammatory and angiogenic fibroproliferative response is accompanied by the presence of abundant mast cells far in excess of other reported myopathies. Results: Using an injury-induced, constitutively-active transgenic mouse model of FOP we show that mast cell inhibition by cromolyn, but not aprepitant, results in a dramatic reduction of heterotopic ossification. Cromolyn, but not aprepitant, significantly decreases the total number of mast cells in FOP lesions. Furthermore, cromolyn specifically diminishes the number of degranulating and resting degranulated mast cells in pre-osseous lesions. Conclusions: This work demonstrates that consideration of FOP as a type of localized mastocytosis may offer new therapeutic interventions for treatment of this devastating condition.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalBone
Volume109
DOIs
StatePublished - Apr 1 2018

Keywords

  • ACVR1
  • Cromolyn
  • Fibrodyplasia ossificans progressiva (FOP)
  • Heterotopic ossification
  • Mast cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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