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Clin Orthop Relat Res. 2014 Feb;472(2):396-404. doi: 10.1007/s11999-013-3325-8. Epub 2013 Oct 18.

Osteogenic gene expression correlates with development of heterotopic ossification in war wounds.

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1
Regenerative Medicine Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.

Abstract

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.

PMID:
24136804
PMCID:
PMC3890153
DOI:
10.1007/s11999-013-3325-8
[Indexed for MEDLINE]
Free PMC Article
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