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Detection of hypoxia inducible factors and angiogenic growth factors during foetal endochondral and intramembranous ossification

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Abstract
During skeletogenesis, the development of a new vascular network, i.e. angiogenesis, is triggered by hypoxia through the activation of the hypoxia inducible factors (HIFs) HIF-1a and HIF-2a. HIFs regulate the expression of several genes, including those coding for angiogenic growth factors such as VEGFA, angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2). The expression of HIFs and angiogenic growth factors is well documented in endochondral ossification, but few data exist on their expression during intramembranous ossification. In this study, the localization of these factors was examined using immunohistochemistry and RT-PCR in bones of porcine foetuses. Immunostaining for HIF-1a and HIF-2a was observed during endochondral ossification, whereas only HIF-2a was present at sites of intramembranous ossification. Furthermore, immunostaining for ANGPT2 was present at sites of endochondral and intramembranous ossification. In addition, gene transcripts for ANGPT1, ANGPT2 and VEGFA were detected with RT-PCR in laser capture microdissected isolates from both types of ossification. These results indicate that angiogenesis plays an important role during endochondral and intramembranous ossification. However, the different expression pattern of theHIF-a subunits suggests that alternative regulatory pathways trigger angiogenesis in these distinct types of ossification.
Keywords
ANGIOPOIETIN-2, VEGF, BONE, OSTEOGENESIS, LIGANDS, SYSTEM, CELLS, HIF-1-ALPHA, MECHANISMS, RECEPTORS

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Chicago
De Spiegelaere, Ward, Pieter Cornillie, Christophe Casteleyn, Christian Burvenich, and Wim Van Den Broeck. 2010. “Detection of Hypoxia Inducible Factors and Angiogenic Growth Factors During Foetal Endochondral and Intramembranous Ossification.” Anatomia Histologia Embryologia 39 (4): 376–384.
APA
De Spiegelaere, W., Cornillie, P., Casteleyn, C., Burvenich, C., & Van Den Broeck, W. (2010). Detection of hypoxia inducible factors and angiogenic growth factors during foetal endochondral and intramembranous ossification. ANATOMIA HISTOLOGIA EMBRYOLOGIA, 39(4), 376–384.
Vancouver
1.
De Spiegelaere W, Cornillie P, Casteleyn C, Burvenich C, Van Den Broeck W. Detection of hypoxia inducible factors and angiogenic growth factors during foetal endochondral and intramembranous ossification. ANATOMIA HISTOLOGIA EMBRYOLOGIA. 2010;39(4):376–84.
MLA
De Spiegelaere, Ward, Pieter Cornillie, Christophe Casteleyn, et al. “Detection of Hypoxia Inducible Factors and Angiogenic Growth Factors During Foetal Endochondral and Intramembranous Ossification.” ANATOMIA HISTOLOGIA EMBRYOLOGIA 39.4 (2010): 376–384. Print.
@article{1163109,
  abstract     = {During skeletogenesis, the development of a new vascular network, i.e. angiogenesis, is triggered by hypoxia through the activation of the hypoxia inducible factors (HIFs) HIF-1a and HIF-2a. HIFs regulate the expression of several genes, including those coding for angiogenic growth factors such as VEGFA, angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2). The expression of HIFs and angiogenic growth factors is well documented in endochondral ossification, but few data exist on their expression during intramembranous ossification.
In this study, the localization of these factors was examined using immunohistochemistry and RT-PCR in bones of porcine foetuses. Immunostaining for HIF-1a and HIF-2a was observed during endochondral ossification, whereas only HIF-2a was present at sites of intramembranous ossification. Furthermore, immunostaining for ANGPT2 was present at sites of endochondral and intramembranous ossification. In addition, gene transcripts for ANGPT1, ANGPT2 and VEGFA were detected with RT-PCR in laser capture microdissected isolates from both types of ossification. These results indicate that angiogenesis plays an important role during endochondral and intramembranous ossification. However, the different expression pattern of theHIF-a subunits suggests that alternative regulatory pathways trigger angiogenesis in these distinct types of ossification.},
  author       = {De Spiegelaere, Ward and Cornillie, Pieter and Casteleyn, Christophe and Burvenich, Christian and Van Den Broeck, Wim},
  issn         = {1439-0264},
  journal      = {ANATOMIA HISTOLOGIA EMBRYOLOGIA},
  keyword      = {ANGIOPOIETIN-2,VEGF,BONE,OSTEOGENESIS,LIGANDS,SYSTEM,CELLS,HIF-1-ALPHA,MECHANISMS,RECEPTORS},
  language     = {eng},
  number       = {4},
  pages        = {376--384},
  title        = {Detection of hypoxia inducible factors and angiogenic growth factors during foetal endochondral and intramembranous ossification},
  url          = {http://dx.doi.org/10.1111/j.1439-0264.2010.01005.x},
  volume       = {39},
  year         = {2010},
}

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