Cytokine expression in muscle following traumatic injury

Wesley M. Jackson, Amber B. Aragon, Jun Onodera, Steven M. Koehler, Youngmi Ji, Jamie D. Bulken-Hoover, Jared A. Vogler, Rocky S. Tuan*, Leon J. Nesti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Heterotopic ossification (HO) occurs at a high frequency in severe orthopaedic extremity injuries; however, the etiology of traumatic HO is virtually unknown. Osteogenic progenitor cells have previously been identified within traumatized muscle. Although the signaling mechanisms that lead to this dysregulated differentiation pathway have not been identified, it is assumed that inflammation and fibrosis, which contribute to an osteoinductive environment, are necessary for the development of HO. The hypothesis of this study was that cytokines related to chronic inflammation, fibrogenesis, and osteogenesis become up-regulated following severe muscle trauma where HO forms. Classification of these cytokines by their differential expression relative to control muscle will provide guidance for further study of the mechanisms leading to HO. Real-time RT-PCR analysis revealed no significant up-regulation of cytokines typically associated with HO (e.g., BMP-4, as observed in the genetic form of HO, fibrodysplasia ossificans progressiva). Instead, the cytokine gene expression profile associated with the traumatized muscle included up-regulation of cytokines associated with osteogenesis and fibrosis (i.e., BMP-1 and TGF-β 1). Using immunohistochemistry, these cytokines were localized to fibroproliferative lesions, which have previously been implicated in HO. This study identifies other cell and tissue-level interactions in traumatized muscle that should be investigated further to better define the etiology of HO.

Original languageEnglish
Pages (from-to)1613-1620
Number of pages8
JournalJournal of Orthopaedic Research
Issue number10
StatePublished - Oct 2011
Externally publishedYes


  • bone morphogenetic protein
  • cytokines
  • gene expression profiling
  • heterotopic ossification
  • muscle injury


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