title: The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in the pathogenesis of heterotopic ossification.
abstract: OBJECTIVE
  Mesenchymal progenitor cells (MPCs) are capable of differentiating into osteo/chondrogenic cells to contribute substantially to heterotopic ossification (HO). This study aimed to examine the impact of hypoxia on MPCs in the aetiology of HO.
  
  
  METHODS
  MPCs from human normal and HO skeletal tissue were cultivated under normoxia and hypoxia. Gene expression of factors which have a key role in HO aetiology (BMPs, COX-1 and COX-2, etc.) were examined by real-time PCR. Tissue of both groups was analysed by immunohistochemistry.
  
  
  RESULTS
  Under hypoxia, COX-1, -2 and SOX-9 gene expression was elevated in HO MPCs, whereas in normal muscle tissue only COX-2 was upregulated. MPCs from HO had a significantly elevated gene expression of BMP-4 and decreased expression of BMP-1 and HIF-1 under hypoxia compared to normal MPCs. Immunohistochemistry detected no significant differences between normal and HO tissue.
  
  
  CONCLUSIONS
  Hypoxia causes an enhanced gene expression of factors, which have a key role in HO pathophysiology. A better understanding of this entity will possibly allow reducing HO rates in orthopaedic and trauma surgery.
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. sebastianwinkler@email.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Winkler
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Tanja.Niedermair@klinik.uni-regensburg.de.|Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany. Tanja.Niedermair@klinik.uni-regensburg.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Niedermair
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, Hospital Barmherzige Brüder, Regensburg, Germany. Bernd.Fuechtmeier@barmherzige-regensburg.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Füchtmeier
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Joachim.Grifka@ukr.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Grifka
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Susanne.Graessel@klinik.uni-regensburg.de.|Centre for Medical Biotechnology, BioPark I, University of Regensburg, Regensburg, Germany. Susanne.Graessel@klinik.uni-regensburg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Grässel
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Sven.Anders@ukr.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Anders
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Guido.Heers@ukr.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Heers
authors.affiliation: Department of Orthopaedic Surgery, Regensburg University Medical Centre, Kaiser-Karl-V Allee 3, 93077, Bad Abbach, Germany. Ferdinand.Wagner@ukr.de.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009999:Ossification, Heterotopic / Q000209:etiology*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
keywords: Heterotopic ossification; Hypoxia; Mesenchymal progenitor cell; Pathogenesis