Expression of angiogenic factors during distraction osteogenesis

D. M. Pacicca, N. Patel, Cassandra A Lee, K. Salisbury, W. Lehmann, R. Carvalho, L. C. Gerstenfeld, T. A. Einhorn

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Distraction osteogenesis is a unique and effective way to treat limb length inequality resulting from congenital and posttraumatic skeletal defects. However, despite its widespread clinical use, the cellular and molecular mechanisms by which this surgical treatment promotes new bone formation are not well understood. Previous studies in distraction osteogenesis have noted increased blood flow and vessel formation within the zone of distraction. These observations suggest that distraction osteogenesis may be driven in part by an angiogenic process. Using immunohistological analysis, the expression of two different angiogenic factors (VEGF and bFGF) was shown to localize at the leading edge of the distraction gap, where nascent osteogenesis was occurring. These cells were spatially adjacent to new vessels that were identified by staining for factor VIII. Microarray analysis detected maximal mRNA expression for a wide variety of angiogenic factors including angiopoietin 1 and 2, both Tie receptors, VEGF-A and -D, VEGFR2, and neuropilin 1. Expression of these factors was found to be maximal during the phase of active distraction. Expression of mRNA for extracellular matrix proteins and BMPs was also maximal during this period. A comparison between the patterns of gene expression in fracture healing and distraction osteogenesis revealed similarities; however, the expression of a number of genes showed selective expression in these two types of bone healing. These data suggest that bone formation during distraction osteogenesis is accompanied by the robust induction of factors associated with angiogenesis and support further investigations to elucidate the mechanisms by which angiogenic events promote bone repair and regeneration.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalBone
Volume33
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Distraction Osteogenesis
Angiogenesis Inducing Agents
Osteogenesis
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor D
Neuropilin-1
Angiopoietin-2
Angiopoietin-1
Messenger RNA
Bone Regeneration
Fracture Healing
Extracellular Matrix Proteins
Factor VIII
Microarray Analysis
Blood Vessels
Extremities
Staining and Labeling
Gene Expression
Bone and Bones
Genes

Keywords

  • Angiogenesis
  • Bone morphogenetic protein
  • Distraction osteogenesis
  • Extracellular matrix
  • mRNA expression

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Pacicca, D. M., Patel, N., Lee, C. A., Salisbury, K., Lehmann, W., Carvalho, R., ... Einhorn, T. A. (2003). Expression of angiogenic factors during distraction osteogenesis. Bone, 33(6), 889-898. https://doi.org/10.1016/j.bone.2003.06.002

Expression of angiogenic factors during distraction osteogenesis. / Pacicca, D. M.; Patel, N.; Lee, Cassandra A; Salisbury, K.; Lehmann, W.; Carvalho, R.; Gerstenfeld, L. C.; Einhorn, T. A.

In: Bone, Vol. 33, No. 6, 12.2003, p. 889-898.

Research output: Contribution to journalArticle

Pacicca, DM, Patel, N, Lee, CA, Salisbury, K, Lehmann, W, Carvalho, R, Gerstenfeld, LC & Einhorn, TA 2003, 'Expression of angiogenic factors during distraction osteogenesis', Bone, vol. 33, no. 6, pp. 889-898. https://doi.org/10.1016/j.bone.2003.06.002
Pacicca DM, Patel N, Lee CA, Salisbury K, Lehmann W, Carvalho R et al. Expression of angiogenic factors during distraction osteogenesis. Bone. 2003 Dec;33(6):889-898. https://doi.org/10.1016/j.bone.2003.06.002
Pacicca, D. M. ; Patel, N. ; Lee, Cassandra A ; Salisbury, K. ; Lehmann, W. ; Carvalho, R. ; Gerstenfeld, L. C. ; Einhorn, T. A. / Expression of angiogenic factors during distraction osteogenesis. In: Bone. 2003 ; Vol. 33, No. 6. pp. 889-898.
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