Effect of age on vascularization during fracture repair

Chuanyong Lu, Erik Hansen, Anna Sapozhnikova, Diane Hu, Theodore Miclau, Ralph S. Marcucio

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4-week-old), middle-aged (6-month-old), and elderly (18-month-old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle-aged and elderly. Hypoxia-inducible factor-la protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle-aged and elderly mice. Stronger Mmp-9 and -13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle-aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle-aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities.

Original languageEnglish (US)
Pages (from-to)1384-1389
Number of pages6
JournalJournal of Orthopaedic Research
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Bony Callus
Blood Vessels
Tibial Fractures
Fracture Healing
Vascular Endothelial Growth Factor A
In Situ Hybridization
Age Groups
Immunohistochemistry
Bone and Bones
Proteins
Therapeutics

Keywords

  • Age
  • Aging
  • Angiogenesis
  • Fracture
  • Vascularization

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Lu, C., Hansen, E., Sapozhnikova, A., Hu, D., Miclau, T., & Marcucio, R. S. (2008). Effect of age on vascularization during fracture repair. Journal of Orthopaedic Research, 26(10), 1384-1389. https://doi.org/10.1002/jor.20667

Effect of age on vascularization during fracture repair. / Lu, Chuanyong; Hansen, Erik; Sapozhnikova, Anna; Hu, Diane; Miclau, Theodore; Marcucio, Ralph S.

In: Journal of Orthopaedic Research, Vol. 26, No. 10, 01.10.2008, p. 1384-1389.

Research output: Contribution to journalArticle

Lu, C, Hansen, E, Sapozhnikova, A, Hu, D, Miclau, T & Marcucio, RS 2008, 'Effect of age on vascularization during fracture repair', Journal of Orthopaedic Research, vol. 26, no. 10, pp. 1384-1389. https://doi.org/10.1002/jor.20667
Lu C, Hansen E, Sapozhnikova A, Hu D, Miclau T, Marcucio RS. Effect of age on vascularization during fracture repair. Journal of Orthopaedic Research. 2008 Oct 1;26(10):1384-1389. https://doi.org/10.1002/jor.20667
Lu, Chuanyong ; Hansen, Erik ; Sapozhnikova, Anna ; Hu, Diane ; Miclau, Theodore ; Marcucio, Ralph S. / Effect of age on vascularization during fracture repair. In: Journal of Orthopaedic Research. 2008 ; Vol. 26, No. 10. pp. 1384-1389.
@article{2270a8f19e334ea4889a6ee146e87fb8,
title = "Effect of age on vascularization during fracture repair",
abstract = "Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4-week-old), middle-aged (6-month-old), and elderly (18-month-old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle-aged and elderly. Hypoxia-inducible factor-la protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle-aged and elderly mice. Stronger Mmp-9 and -13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle-aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle-aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities.",
keywords = "Age, Aging, Angiogenesis, Fracture, Vascularization",
author = "Chuanyong Lu and Erik Hansen and Anna Sapozhnikova and Diane Hu and Theodore Miclau and Marcucio, {Ralph S.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1002/jor.20667",
language = "English (US)",
volume = "26",
pages = "1384--1389",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Effect of age on vascularization during fracture repair

AU - Lu, Chuanyong

AU - Hansen, Erik

AU - Sapozhnikova, Anna

AU - Hu, Diane

AU - Miclau, Theodore

AU - Marcucio, Ralph S.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4-week-old), middle-aged (6-month-old), and elderly (18-month-old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle-aged and elderly. Hypoxia-inducible factor-la protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle-aged and elderly mice. Stronger Mmp-9 and -13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle-aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle-aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities.

AB - Age affects fracture repair; however, the underlying mechanisms are not well understood. The goal of this study was to assess the effects that age has on vascularization during fracture healing. Tibial fractures were created in juvenile (4-week-old), middle-aged (6-month-old), and elderly (18-month-old) mice. The length density and surface density of blood vessels within fracture calluses were analyzed using stereology at 7 days after fracture. The expression of molecules that regulate vascular invasion of the fracture callus was also compared among the three age groups by immunohistochemistry and in situ hybridization. At 7 days after fracture, juvenile mice had a higher surface density of blood vessels compared to the middle-aged and elderly. Hypoxia-inducible factor-la protein and transcripts of vascular endothelial growth factor were detected at 3 days postinjury in juvenile but not middle-aged and elderly mice. Stronger Mmp-9 and -13 expression was detected in fracture calluses at day 7 in the juvenile compared to the middle-aged and elderly mice. At 21 days postfracture, expression of both Mmps was more robust in the elderly than juvenile and middle-aged animals. These data indicate that age affects vascularization during fracture repair, and the changes we observed are directly correlated with altered expression of biochemical factors that regulate the process of angiogenesis. However, whether the increased vascularization is the cause or result of accelerated bone repair in juvenile animals remains unknown. Nonetheless, our results indicate that enhancing vascularization during fracture repair in the elderly may provide unique therapeutic opportunities.

KW - Age

KW - Aging

KW - Angiogenesis

KW - Fracture

KW - Vascularization

UR - http://www.scopus.com/inward/record.url?scp=53549103875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53549103875&partnerID=8YFLogxK

U2 - 10.1002/jor.20667

DO - 10.1002/jor.20667

M3 - Article

C2 - 18464248

AN - SCOPUS:53549103875

VL - 26

SP - 1384

EP - 1389

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 10

ER -