Effects of Bone Morphogenetic Protein-2 on Neovascularization during Large Bone Defect Regeneration

Hope B. Pearson, Devon E. Mason, Christopher D. Kegelman, Liming Zhao, James H. Dawahare, Melissa A. Kacena, Joel D. Boerckel

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large bone defect repair. Recombinant bone morphogenetic protein-2 (BMP-2) delivery induces robust bone formation and has been observed to enhance neovascularization, but whether the angiogenic effects of BMP-2 are due to direct endothelial cell stimulation or due to indirect paracrine signaling remain unclear. In this study, we evaluated the effects of BMP-2 delivery on vascularized bone regeneration and tested whether BMP-2 induces neovascularization directly or indirectly. We found that delivery of BMP-2 (5 μg) enhanced both bone formation and neovascularization in critically sized (8 mm) rat femoral bone defects; however, BMP-2 did not directly stimulate angiogenesis in vitro. In contrast, conditioned medium from both mesenchymal progenitor cells and osteoblasts induced endothelial cell migration in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, codelivery of BMP-2 with endothelial colony forming cells to a heterotopic site, distant from the skeletal stem cell-rich bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that paracrine activation of osteoprogenitor cells is an important contributor to neovascularization during BMP-2-mediated bone regeneration.

Original languageEnglish (US)
Pages (from-to)1623-1634
Number of pages12
JournalTissue Engineering - Part A
Volume25
Issue number23-24
DOIs
StatePublished - Dec 2019

Keywords

  • BMP-2
  • angiogenesis
  • bone defect
  • bone regeneration

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint Dive into the research topics of 'Effects of Bone Morphogenetic Protein-2 on Neovascularization during Large Bone Defect Regeneration'. Together they form a unique fingerprint.

  • Cite this

    Pearson, H. B., Mason, D. E., Kegelman, C. D., Zhao, L., Dawahare, J. H., Kacena, M. A., & Boerckel, J. D. (2019). Effects of Bone Morphogenetic Protein-2 on Neovascularization during Large Bone Defect Regeneration. Tissue Engineering - Part A, 25(23-24), 1623-1634. https://doi.org/10.1089/ten.tea.2018.0326