title: Human early fracture hematoma is characterized by inflammation and hypoxia.
abstract: BACKGROUND
  An effective immune system, especially during the inflammatory phase, putatively influences the quality and likelihood of bone healing. If and how this is reflected within the initial fracture hematoma is unclear.
  
  
  OBJECTIVE
  We therefore asked the following questions: (1) Does the local expression in fracture hematoma of genes involved in adaptation to hypoxia, migration, angiogenesis, and osteogenesis vary as compared to the peripheral blood? (2) Do these changes occur time dependently? (3) Is the gene expression during fracture hematoma formation altered by irradiation?
  
  
  METHODS
  Cells from fracture hematoma of 20 patients and hematomas formed in 40 patients after THA (20 without and 20 with preoperative radiation) were isolated and RNA was extracted to analyze the influence of oxygen deprivation during fracture healing on mRNA expression of genes (HIF1A, LDHA, and PGK1) involved in immunoregulation (IL6, IL8, CXCR4), angiogenesis (VEGF, IL8), and osteogenesis (SPP1, RUNX2) by quantitative PCR.
  
  
  RESULTS
  We observed locally increased LDHA gene expression in fracture hematoma cells (6-72 h post fracture) reflecting the adaptation to hypoxia. IL6, IL8, and VEGF upregulation indicated hypoxia-mediated inflammation and angiogenesis; increased CXCR4 expression reflected immigration of immune cells. Osteogenic differentiation was reflected in the increased expression of the SPP1 and RUNX2 genes. The increased expression of the LDHA, VEGF, IL8, SPP1 and RUNX2 genes occurred time dependently. Irradiation suppressed HIF1A, IL6, IL8, CXCR4, and RUNX2 gene expression.
  
  
  CONCLUSIONS
  Our data suggest cells in the fracture hematoma (1) adapt to hypoxia and (2) promote inflammation in fracture healing at the mRNA level, indicating early involvement of the immune system.
  
  
  CONCLUSIONS
  The initial fracture hematoma is important for the onset of angiogenesis, chemotaxis, and osteogenesis.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Charitéplatz 1, 10117 Berlin, Germany. paula.kolar@charite.de
authors.forename: Paula
authors.initials: P
authors.lastname: Kolar
authors.forename: Timo
authors.initials: T
authors.lastname: Gaber
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001861:Bone Regeneration / Q000502:physiology; D015687:Cell Hypoxia / Q000235:genetics* / Q000276:immunology; D005260:Female; D017102:Fracture Healing; D005596:Fractures, Closed / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D006406:Hematoma / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A