TY - JOUR
T1 - Osteogenic gene expression correlates with development of heterotopic ossification in war wounds
AU - Evans, Korboi N.
AU - Potter, Benjamin K.
AU - Brown, Trevor S.
AU - Davis, Thomas A.
AU - Elster, Eric A.
AU - Forsberg, Jonathan A.
N1 - Funding Information:
Funding for this study was received from the US Navy Bureau of Medicine and Surgery under the Medical Development Program (PE 0604771 N, Principal Investigator EAE). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, the Department of the Navy, Department of Defense, nor the US Government. This work was funded by work unit number 601153 N.4508.5180.A0508. The authors are military service members (or employees of the US Government). This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that ‘‘Copyright protection under this title is not available for any work of the United States Government.’’ Title 17 U.S.C. 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties. This work was performed at the Walter Reed National Military Medical Center and the Naval Medical Research Center, Bethesda, MD, USA.
PY - 2014/2
Y1 - 2014/2
N2 - Background: Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes: The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods: Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Results: The transcripts of 13 genes (ALPL [p = 0.006], BMP-2 [p < 0.001], BMP-3 [p = 0.06], COL2A1 [p < 0.001], COLL10A1 [p < 0.001], COL11A1 [p = 0.006], COMP [p = 0.02], CSF2 [p = 0.003], CSF3 [p = 0.012], MMP8 [p < 0.001], MMP9 [p = 0.014], SMAD1 [p = 0.024], and VEGFA [p = 0.017]) were upregulated greater than twofold in wounds in which HO developed compared with wounds in which it did not develop. Gene transcript expression of BMP-2 also correlated directly with functional protein expression in the wounds that formed HO (p = 0.029). Conclusions: Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds. Clinical Relevance: Understanding the osteogenic environment associated with war wounds may allow for the development of novel therapeutic strategies for HO.
AB - Background: Heterotopic ossification (HO) is a frequent complication of modern wartime extremity injuries. The biological mechanisms responsible for the development of HO in traumatic wounds remain elusive. Question/purposes: The aims of our study were to (1) characterize the expression profile of osteogenesis-related gene transcripts in traumatic war wounds in which HO developed; and (2) determine whether expression at the mRNA level correlated with functional protein expression and HO formation. Methods: Biopsy specimens from 54 high-energy penetrating extremity wounds obtained at the initial and final surgical débridements were evaluated. The levels of selected osteogenic-related gene transcripts from RNA extracts were assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. As a result of its key role in osteogenesis, the concentration of BMP-2 in the effluent of 29 wounds also was determined. Results: The transcripts of 13 genes (ALPL [p = 0.006], BMP-2 [p < 0.001], BMP-3 [p = 0.06], COL2A1 [p < 0.001], COLL10A1 [p < 0.001], COL11A1 [p = 0.006], COMP [p = 0.02], CSF2 [p = 0.003], CSF3 [p = 0.012], MMP8 [p < 0.001], MMP9 [p = 0.014], SMAD1 [p = 0.024], and VEGFA [p = 0.017]) were upregulated greater than twofold in wounds in which HO developed compared with wounds in which it did not develop. Gene transcript expression of BMP-2 also correlated directly with functional protein expression in the wounds that formed HO (p = 0.029). Conclusions: Important differences exist in the osteogenic gene expression profile of wounds in which HO developed compared with wounds in which it did not develop. The upregulation of multiple osteogenesis-related gene transcripts indicates the presence of a proosteogenic environment necessary for ectopic bone formation in traumatic wounds. Clinical Relevance: Understanding the osteogenic environment associated with war wounds may allow for the development of novel therapeutic strategies for HO.
UR - http://www.scopus.com/inward/record.url?scp=84893645277&partnerID=8YFLogxK
U2 - 10.1007/s11999-013-3325-8
DO - 10.1007/s11999-013-3325-8
M3 - Article
C2 - 24136804
AN - SCOPUS:84893645277
SN - 0009-921X
VL - 472
SP - 396
EP - 404
JO - Clinical Orthopaedics and Related Research
JF - Clinical Orthopaedics and Related Research
IS - 2
ER -