Effects of Bone Morphogenetic Protein-2 on Neovascularization During Large Bone Defect Regeneration
| العنوان: | Effects of Bone Morphogenetic Protein-2 on Neovascularization During Large Bone Defect Regeneration |
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| المؤلفون: | Christopher D Kegelman, Hope B Pearson, Joel D. Boerckel, Liming Zhao, Devon E. Mason, James H. Dawahare, Melissa A. Kacena |
| المصدر: | Tissue Eng Part A |
| بيانات النشر: | Mary Ann Liebert Inc, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Bone Regeneration, Angiogenesis, Biomedical Engineering, Bone Morphogenetic Protein 2, Neovascularization, Physiologic, Bioengineering, Choristoma, Biochemistry, Bone morphogenetic protein 2, Colony-Forming Units Assay, Rats, Sprague-Dawley, Biomaterials, Neovascularization, Mice, Cell Movement, Osteogenesis, Animals, Humans, Medicine, Femur, Bone regeneration, Osteoblasts, business.industry, Regeneration (biology), Endothelial Cells, Mesenchymal Stem Cells, Original Articles, Bone defect, Cell biology, medicine.anatomical_structure, Culture Media, Conditioned, Female, medicine.symptom, business, Blood vessel |
| الوصف: | 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. IMPACT STATEMENT: In this study, we show that bone morphogenetic protein-2 (BMP-2) robustly induces neovascularization during tissue-engineered large bone defect regeneration, and we found that BMP-2 induced angiogenesis, in part, through paracrine signaling from osteoprogenitor cells. |
| تدمد: | 1937-335X 1937-3341 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40f011afb5099b5e942a4d28c1c6a310 https://doi.org/10.1089/ten.tea.2018.0326 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....40f011afb5099b5e942a4d28c1c6a310 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1937335X 19373341 |
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