Tissue-Specific Stem Cells

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Dysregulation of Local Stem/Progenitor Cells as a Common Cellular Mechanism for Heterotopic Ossification†‡§

  1. Lixin Kan1,¶,*,
  2. Yijie Liu1,
  3. Tammy L. McGuire1,
  4. Diana M. Palila Berger2,
  5. Rajeshwar B. Awatramani1,
  6. Susan M. Dymecki3,
  7. John A. Kessler1

Article first published online: 5 JAN 2009

DOI: 10.1634/stemcells.2008-0576

Issue

STEM CELLS

STEM CELLS

Volume 27, Issue 1, pages 150–156, January 2009

Additional Information

How to Cite

Kan, L., Liu, Y., McGuire, T. L., Berger, D. M. P., Awatramani, R. B., Dymecki, S. M. and Kessler, J. A. (2009), Dysregulation of Local Stem/Progenitor Cells as a Common Cellular Mechanism for Heterotopic Ossification. STEM CELLS, 27: 150–156. doi: 10.1634/stemcells.2008-0576

Author Information

  1. 1

    Department of Neurology, Northwestern University Feinberg Medical School, Chicago, Illinois

  2. 2

    Center for Comparative Medicine, Northwestern University Feinberg Medical School, Chicago, Illinois

  3. 3

    Department of Genetics, Harvard Medical School, Boston, Massachusetts

  1. Telephone: 312-503-2793; Fax: 312-503-2799

*Northwestern University Feinberg School of Medicine, Ward Building 10-185, 303 East Chicago Avenue, Chicago, Illinois 60611-3008

  1. †

    Author contributions: L.K.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; Y.L., T.M., and D.P.B.: collection and/or assembly of data; R.B.A. and S.M.D.: provision of study material; J.A.K.: conception and design, financial support, data analysis and interpretation, final approval of manuscript, administrative support.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSExpress October 2, 2008.

Publication History

  1. Issue published online: 5 JAN 2009
  2. Article first published online: 5 JAN 2009
  3. Manuscript Accepted: 22 SEP 2008
  4. Manuscript Received: 17 JUN 2008

Funded by

  • The Center for Research in FOP
  • Related Disorders of The University of Pennsylvania School of Medicine
  • NIH. Grant Numbers: NS20013, NS20778

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Keywords:

  • Heterotopic ossification;
  • Fibrodysplasia ossificans progressiva;
  • Nse-BMP4;
  • Macrophages

Abstract

Heterotopic ossification (HO), the abnormal formation of true marrow-containing bone within extraskeletal soft tissues, is a serious bony disorder that may be either acquired or hereditary. We utilized an animal model of the genetic disorder fibrodysplasia ossificans progressiva to examine the cellular mechanisms underlying HO. We found that HO in these animals was triggered by soft tissue injuries and that the effects were mediated by macrophages. Spreading of HO beyond the initial injury site was mediated by an abnormal adaptive immune system. These observations suggest that dysregulation of local stem/progenitor cells could be a common cellular mechanism for typical HO irrespective of the signal initiating the bone formation. STEM CELLS2009;27:150–156

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