The role of oxygen during fracture healing.
Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing. However, the role of oxygen in fracture healing has not been fully studied. Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects in a mouse model of ischemic fracture healing. Mice with tibia fracture were housed in custom-built gas chambers and groups breathed a constant atmosphere of 13% oxygen (hypoxia), 21% oxygen (normoxia), or 50% oxygen (hyperoxia). The influx of inflammatory cells to the fracture site, stem cell differentiation, tissue vascularization, and fracture healing were analyzed. In addition, the efficacy of hyperoxia (50% oxygen) as a treatment regimen for fracture nonunion was tested. Hypoxic animals had decreased tissue vascularity, decreased bone formation, and delayed callus remodeling. Hyperoxia increased tissue vascularization, altered fracture healing in un-complicated fractures, and improved bone repair in ischemia-induced delayed fracture union. However, neither hypoxia nor hyperoxia significantly altered chondrogenesis or osteogenesis during early stages of fracture healing, and infiltration of macrophages and neutrophils was not affected by environmental oxygen after bone injury. In conclusion, our results indicate that environmental oxygen levels affect tissue vascularization and fracture healing, and that providing oxygen when fractures are accompanied by ischemia may be beneficial.
Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, San Francisco General Hospital, University of California at San Francisco, 1001 Potrero Ave., San Francisco, CA 94110, USA.
Chuanyong
C
Lu
Neema
N
Saless
Xiaodong
X
Wang
Arjun
A
Sinha
Sebastian
S
Decker
Galateia
G
Kazakia
Huagang
H
Hou
Benjamin
B
Williams
Harold M
HM
Swartz
Thomas K
TK
Hunt
Theodore
T
Miclau
Ralph S
RS
Marcucio
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D017102:Fracture Healing / Q000502:physiology*; D051379:Mice; D010100:Oxygen / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen