Effects of BMP-2 on neovascularization during large bone defect regeneration



Insufficient blood vessel supply is a primary limiting factor for regenerative approaches to large bone defect repair. Recombinant 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 to indirect paracrine signaling remains unclear. Here, 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 angiogenesis in vitro, suggesting a paracrine mechanism of BMP-2 action. Consistent with this inference, co-delivery of BMP-2 with endothelial colony forming cells (ECFCs) to a heterotopic site, distant from the bone marrow niche, induced ossification but had no effect on neovascularization. Taken together, these data suggest that BMP-2 induces neovascularization during bone regeneration primarily through paracrine activation of osteoprogenitor cells.


Attribute NameValues
  • Hope Pearson

  • Devon Mason

  • Christopher Kegelman

  • Liming Zhao

  • James Dawahare

  • Melissa Kacena

  • Joel Boerckel

Journal or Work Title
  • Tissue Engineering: Part A

  • 1937-3341

Publication Date
  • 2019-09

  • Magellan SEM


Date Created
  • 2019-09-12

  • English

Departments and Units
Record Visibility Public
Content License
  • All rights reserved

Digital Object Identifier


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