Inflammation in Fibrodysplasia Ossificans Progressiva and Other Forms of Heterotopic Ossification

  • Koji Matsuo
  • Robert Dalton Chavez
  • Emilie Barruet
  • Edward C. HsiaoEmail author
Osteoimmunology (M Nakamura and J Lorenzo, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Osteoimmunology


Purpose of review

Heterotopic ossification (HO) is associated with inflammation. The goal of this review is to examine recent findings on the roles of inflammation and the immune system in HO. We examine how inflammation changes in fibrodysplasia ossificans progressiva, in traumatic HO, and in other clinical conditions of HO. We also discuss how inflammation may be a target for treating HO.

Recent findings

Both genetic and acquired forms of HO show similarities in their inflammatory cell types and signaling pathways. These include macrophages, mast cells, and adaptive immune cells, along with hypoxia signaling pathways, mesenchymal stem cell differentiation signaling pathways, vascular signaling pathways, and inflammatory cytokines.


Because there are common inflammatory mediators across various types of HO, these mediators may serve as common targets for blocking HO. Future research may focus on identifying new inflammatory targets and testing combinatorial therapies based on these results.


Heterotopic ossification Inflammation Immune activation Macrophages Cytokines 



The authors thank Mary Nakamura for critical advice on this manuscript. ECH received support from 1R01AR066735 and 1R01AR073015. RDC received support from 5R21AR072778.

Compliance with Ethical Standards

Conflict of Interest

Edward Hsiao serves on the registry advisory board of the International Fibrodysplasia Ossificans Progressiva Association, is on the International Clinical Council on FOP, and is on the Fibrous Dysplasia Foundation Medical Advisory Board. ECH receives clinical trials research support through his institution from Clementia Pharmaceuticals Inc. to support clinical trials of palovarotene in FOP. ECH previously received clinical trials support through his institution from Regeneron Pharmaceuticals, Inc. These pose no conflicts for this study.

Koji Matsuo, Robert Dalton Chavez, and Emilie Barruet declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Koji Matsuo
    • 1
    • 2
    • 3
  • Robert Dalton Chavez
    • 1
    • 2
    • 3
  • Emilie Barruet
    • 1
    • 2
    • 3
  • Edward C. Hsiao
    • 1
    • 2
    • 3
    Email author
  1. 1.Division of Endocrinology and MetabolismUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Medicine, The Institute for Human GeneticsUniversity of CaliforniaSan FranciscoUSA
  3. 3.The Program in Craniofacial BiologyUniversity of CaliforniaSan FranciscoUSA

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