The role of oxygen during fracture healing

Chuanyong Lu, Neema Saless, Xiaodong Wang, Arjun Sinha, Sebastian Decker, Galateia Kazakia, Huagang Hou, Benjamin Williams, Harold M. Swartz, Thomas K. Hunt, Theodore Miclau, Ralph S. Marcucio

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)220-229
Number of pages10
JournalBone
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Fracture Healing
Oxygen
Hyperoxia
Osteogenesis
Ischemia
Chondrogenesis
Neutrophil Infiltration
Bone Fractures
Bony Callus
Tibia
Atmosphere
Cell Differentiation
Stem Cells
Gases
Macrophages
Bone and Bones

Keywords

  • Angiogenesis
  • Fracture
  • Hyperoxia
  • Hypoxia
  • Oxygen

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Lu, C., Saless, N., Wang, X., Sinha, A., Decker, S., Kazakia, G., ... Marcucio, R. S. (2013). The role of oxygen during fracture healing. Bone, 52(1), 220-229. https://doi.org/10.1016/j.bone.2012.09.037

The role of oxygen during fracture healing. / Lu, Chuanyong; Saless, Neema; Wang, Xiaodong; Sinha, Arjun; Decker, Sebastian; Kazakia, Galateia; Hou, Huagang; Williams, Benjamin; Swartz, Harold M.; Hunt, Thomas K.; Miclau, Theodore; Marcucio, Ralph S.

In: Bone, Vol. 52, No. 1, 01.01.2013, p. 220-229.

Research output: Contribution to journalArticle

Lu, C, Saless, N, Wang, X, Sinha, A, Decker, S, Kazakia, G, Hou, H, Williams, B, Swartz, HM, Hunt, TK, Miclau, T & Marcucio, RS 2013, 'The role of oxygen during fracture healing', Bone, vol. 52, no. 1, pp. 220-229. https://doi.org/10.1016/j.bone.2012.09.037
Lu C, Saless N, Wang X, Sinha A, Decker S, Kazakia G et al. The role of oxygen during fracture healing. Bone. 2013 Jan 1;52(1):220-229. https://doi.org/10.1016/j.bone.2012.09.037
Lu, Chuanyong ; Saless, Neema ; Wang, Xiaodong ; Sinha, Arjun ; Decker, Sebastian ; Kazakia, Galateia ; Hou, Huagang ; Williams, Benjamin ; Swartz, Harold M. ; Hunt, Thomas K. ; Miclau, Theodore ; Marcucio, Ralph S. / The role of oxygen during fracture healing. In: Bone. 2013 ; Vol. 52, No. 1. pp. 220-229.
@article{d06eff13a875417480053e2e53596ec6,
title = "The role of oxygen during fracture healing",
abstract = "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.",
keywords = "Angiogenesis, Fracture, Hyperoxia, Hypoxia, Oxygen",
author = "Chuanyong Lu and Neema Saless and Xiaodong Wang and Arjun Sinha and Sebastian Decker and Galateia Kazakia and Huagang Hou and Benjamin Williams and Swartz, {Harold M.} and Hunt, {Thomas K.} and Theodore Miclau and Marcucio, {Ralph S.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.bone.2012.09.037",
language = "English (US)",
volume = "52",
pages = "220--229",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - The role of oxygen during fracture healing

AU - Lu, Chuanyong

AU - Saless, Neema

AU - Wang, Xiaodong

AU - Sinha, Arjun

AU - Decker, Sebastian

AU - Kazakia, Galateia

AU - Hou, Huagang

AU - Williams, Benjamin

AU - Swartz, Harold M.

AU - Hunt, Thomas K.

AU - Miclau, Theodore

AU - Marcucio, Ralph S.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Fracture

KW - Hyperoxia

KW - Hypoxia

KW - Oxygen

UR - http://www.scopus.com/inward/record.url?scp=84867897196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867897196&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2012.09.037

DO - 10.1016/j.bone.2012.09.037

M3 - Article

C2 - 23063782

AN - SCOPUS:84867897196

VL - 52

SP - 220

EP - 229

JO - Bone

JF - Bone

SN - 8756-3282

IS - 1

ER -