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Heterotopic Ossification Following Musculoskeletal Trauma: Modeling Stem and Progenitor Cells in Their Microenvironment

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Human Cell Transformation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 720))

Abstract

Heterotopic ossification (HO), characterized by the formation of mature bone in the soft tissues, is a complication that can accompany musculoskeletal injury, and it is a frequent occurrence within the military population that has experienced orthopaedic combat trauma. The etiology of this disease is largely unknown. Our laboratory has developed strategies to investigate the cellular and molecular events leading to HO using clinical specimens that were obtained during irrigation and debridement of musculoskeletal injuries. Our approach enables to study (1) the cell types that are responsible for pathological transformation and ossification, (2) the cell- and tissue-level signaling that induces the pathologic transformation, and (3) the effect of extracellular matrix topography and force transduction on HO progression. In this review, we will report on our findings in each of these aspects of HO etiology and describe our efforts to recapitulate our findings in an animal model for traumatic HO.

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Acknowledgements

This work was supported acknowledged as part of the NIH Intramural Research Program. (Z01 AR41131 and 1ZIAAR041191), grants from the Department of Defense Military Amputee Research Program at WRAMC (PO5-A011), Comprehensive Neurosci­ences Program (CNP-2008-CR01) and Peer-Reviewed Orthopaedic Research Program (W81XWH-10-2-0084).

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Authors and Affiliations

  1. Clinical and Experimental Orthopaedics Group, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Youngmi Ji, Gregory T. Christopherson, Matthew W. Kluk & Orna Amrani

  2. Integrated Department of Orthopaedics and Rehabilitation, Walter Reed Army Medical and National Naval Medical Center, Bethesda, MD, USA

    Matthew W. Kluk & Leon J. Nesti

  3. Clinical and Experimental Orthopaedics Laboratory, Department of Surgery, The Uniformed Services University, Bethesda, MD, USA

    Wesley M. Jackson

  4. Clinical and Experimental Orthopaedics Group, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1525, 50 South Drive, MSC 8022, Bethesda, MD, 20892-8022, USA

    Leon J. Nesti

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  1. Youngmi Ji
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  2. Gregory T. Christopherson
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  3. Matthew W. Kluk
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  4. Orna Amrani
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  6. Leon J. Nesti
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Correspondence to Leon J. Nesti .

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Editors and Affiliations

  1. Uniformed Services, Department of Surgery, University of the Health Sciences, South Glen Road 11455, Bethesda, 20854, Maryland, USA

    Johng S. Rhim

  2. , Department of Medicine, McGill University Health Centre, Pine Ave 687, Montreal, Québec, Canada

    Richard Kremer

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Ji, Y., Christopherson, G.T., Kluk, M.W., Amrani, O., Jackson, W.M., Nesti, L.J. (2011). Heterotopic Ossification Following Musculoskeletal Trauma: Modeling Stem and Progenitor Cells in Their Microenvironment. In: Rhim, J., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 720. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0254-1_4

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