title: Cytokine expression in muscle following traumatic injury.
abstract: 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.
authors: Cartilage Biology and Orthopaedic Branch, Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, 50 South Dr, Room 1140, MSC 8022, Bethesda, Maryland, USA.
authors: Wesley M
authors: WM
authors: Jackson
authors: Amber B
authors: AB
authors: Aragon
authors: Jun
authors: J
authors: Onodera
authors: Steven M
authors: SM
authors: Koehler
authors: Youngmi
authors: Y
authors: Ji
authors: Jamie D
authors: JD
authors: Bulken-Hoover
authors: Jared A
authors: JA
authors: Vogler
authors: Rocky S
authors: RS
authors: Tuan
authors: Leon J
authors: LJ
authors: Nesti
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism; D009221:Myositis Ossificans / Q000235:genetics; D009999:Ossification, Heterotopic / Q000209:etiology / Q000378:metabolism*; D017695:Soft Tissue Injuries / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines