Table of Contents
Bone Marrow Research
Volume 2013, Article ID 737580, 9 pages
http://dx.doi.org/10.1155/2013/737580
Research Article

Adenoviral Delivery of the VEGF and BMP-6 Genes to Rat Mesenchymal Stem Cells Potentiates Osteogenesis

Orthopaedic Research Laboratories, Department of Orthopedic Surgery, University of Virginia School of Medicine, P.O. Box 800159, Charlottesville, VA 22908, USA

Received 29 October 2012; Accepted 18 December 2012

Academic Editor: Peter J. Quesenberry

Copyright © 2013 Jesse Seamon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Chen, M. Zhao, and G. R. Mundy, “Bone morphogenetic proteins,” Growth Factors, vol. 22, no. 4, pp. 233–241, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Ebisawa, K. Tada, I. Kitajima et al., “Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation,” Journal of Cell Science, vol. 112, pp. 3519–3527, 1999. View at Google Scholar · View at Scopus
  3. T. A. Einhorn, R. J. O'Keefe, and J. A. Buckwalter, Orthopaedic Basic Science: Foundations of Clinical Practice, American Academy of Orthopaedic Surgeons, 2007.
  4. A. C. Akman, R. S. Tiǧli, M. Gumusderelioglu, and R. M. Nohutcu, “Bone morphogenetic protein-6-loaded chitosan scaffolds enhance the osteoblastic characteristics of MC3T3-E1 cells,” Artificial Organs, vol. 34, no. 1, pp. 65–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. N. Bachl, W. Derman, L. Engebretsen et al., “Therapeutic use of growth factors in the musculoskeletal system in sports-related injuries,” Journal of Sports Medicine and Physical Fitness, vol. 49, no. 4, pp. 346–357, 2009. View at Google Scholar · View at Scopus
  6. A. L. Bertone, D. D. Pittman, M. L. Bouxsein, J. Li, B. Clancy, and H. J. Seeherman, “Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model,” Journal of Orthopaedic Research, vol. 22, no. 6, pp. 1261–1270, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. C. F. Dilling, A. M. Wada, Z. W. Lazard et al., “Vessel formation is induced prior to the appearance of cartilage in BMP-2-mediated heterotopic ossification,” Journal of Bone and Mineral Research, vol. 25, no. 5, pp. 1147–1156, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Fajardo, C. J. Liu, and K. Egol, “Levels of expression for BMP-7 and several BMP antagonists may play an integral role in a fracture nonunion: a pilot study,” Clinical Orthopaedics and Related Research, vol. 467, no. 12, pp. 3071–3078, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. F. Cui, X. Wang, X. Liu, A. S. Dighe, G. Balian, and Q. Cui, “VEGF and BMP-6 enhance bone formation mediated by cloned mouse osteoprogenitor cells,” Growth Factors, vol. 28, no. 5, pp. 306–317, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. W. A. Grasser, I. Orlic, F. Borovecki et al., “BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways,” International Orthopaedics, vol. 31, no. 6, pp. 759–765, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Hou, X. Zhang, T. Tang, K. Dai, and R. Ge, “Enhancement of bone formation by genetically-engineered bone marrow stromal cells expressing BMP-2, VEGF and angiopoietin-1,” Biotechnology Letters, vol. 31, no. 8, pp. 1183–1189, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. A. Ishihara, K. M. Shields, A. S. Litsky et al., “Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models,” Journal of Orthopaedic Research, vol. 26, no. 6, pp. 764–771, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. J. M. Kanczler, P. J. Ginty, L. White et al., “The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to osteoprogenitor cell populations on bone formation,” Biomaterials, vol. 31, no. 6, pp. 1242–1250, 2010. View at Publisher · View at Google Scholar · View at Scopus
  14. Q. Kang, M. H. Sun, H. Cheng et al., “Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery,” Gene Therapy, vol. 11, no. 17, pp. 1312–1320, 2004. View at Publisher · View at Google Scholar · View at Scopus
  15. D. H. R. Kempen, L. Lu, A. Heijink et al., “Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration,” Biomaterials, vol. 30, no. 14, pp. 2816–2825, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Lammens, Z. Liu, and F. Luyten, “Bone morphogenetic protein signaling in the murine distraction osteogenesis model,” Acta Orthopaedica Belgica, vol. 75, no. 1, pp. 94–102, 2009. View at Google Scholar · View at Scopus
  17. K. Lavery, P. Swain, D. Falb, and M. H. Alaoui-Ismaili, “BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells,” The Journal of Biological Chemistry, vol. 283, no. 30, pp. 20948–20958, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Z. Li, H. Li, T. Sasaki et al., “Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat,” Gene Therapy, vol. 10, no. 20, pp. 1735–1743, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. H. H. Luu, W. X. Song, X. Luo et al., “Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells,” Journal of Orthopaedic Research, vol. 25, no. 5, pp. 665–677, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. R. Marsell and T. A. Einhorn, “The role of endogenous bone morphogenetic proteins in normal skeletal repair,” Injury, vol. 40, supplement 3, pp. S4–S7, 2009. View at Google Scholar · View at Scopus
  21. Z. S. Patel, S. Young, Y. Tabata, J. A. Jansen, M. E. K. Wong, and A. G. Mikos, “Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model,” Bone, vol. 43, no. 5, pp. 931–940, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Peng, A. Usas, A. Olshanski et al., “VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis,” Journal of Bone and Mineral Research, vol. 20, no. 11, pp. 2017–2027, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Peng, V. Wright, A. Usas et al., “Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4,” Journal of Clinical Investigation, vol. 110, no. 6, pp. 751–759, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Samee, S. Kasugai, H. Kondo, K. Ohya, H. Shimokawa, and S. Kuroda, “Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation,” Journal of Pharmacological Sciences, vol. 108, no. 1, pp. 18–31, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. J. Street, M. Bao, L. DeGuzman et al., “Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 15, pp. 9656–9661, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Vukicevic and L. Grgurevic, “BMP-6 and mesenchymal stem cell differentiation,” Cytokine and Growth Factor Reviews, vol. 20, no. 5-6, pp. 441–448, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. E. A. Wang, V. Rosen, J. S. D'Alessandro et al., “Recombinant human bone morphogenetic protein induces bone formation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 6, pp. 2220–2224, 1990. View at Google Scholar · View at Scopus
  28. S. Young, Z. S. Patel, J. D. Kretlow et al., “Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model,” Tissue Engineering A, vol. 15, no. 9, pp. 2347–2362, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. T. A. Zachos, K. M. Shields, and A. L. Bertone, “Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6,” Journal of Orthopaedic Research, vol. 24, no. 6, pp. 1279–1291, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. F. Geiger, H. Lorenz, W. Xu et al., “VEGF producing bone marrow stromal cells (BMSC) enhance vascularization and resorption of a natural coral bone substitute,” Bone, vol. 41, no. 4, pp. 516–522, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. M. O. Hiltunen, M. Ruuskanen, J. Huuskonen et al., “Adenovirus-mediated VEGF-A gene transfer induces bone formation in vivo,” The FASEB Journal, vol. 17, no. 9, pp. 1147–1149, 2003. View at Google Scholar · View at Scopus
  32. D. M. Pacicca, N. Patel, C. Lee et al., “Expression of angiogenic factors during distraction osteogenesis,” Bone, vol. 33, no. 6, pp. 889–898, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. C. J. Wang, K. E. Huang, Y. C. Sun et al., “VEGF modulates angiogenesis and osteogenesis in shockwave-promoted fracture healing in rabbits,” Journal of Surgical Research, vol. 171, no. 1, pp. 114–119, 2010. View at Google Scholar
  34. P. Simic, J. B. Culej, I. Orlic et al., “Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption,” The Journal of Biological Chemistry, vol. 281, no. 35, pp. 25509–25521, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Garimella, S. E. Tague, J. Zhang et al., “Expression and synthesis of bone morphogenetic proteins by osteoclasts: a possible path to anabolic bone remodeling,” Journal of Histochemistry and Cytochemistry, vol. 56, no. 6, pp. 569–577, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Wutzl, W. Brozek, I. Lernbass et al., “Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation,” Journal of Biomedical Materials Research A, vol. 77, no. 1, pp. 75–83, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Song, C. Krause, S. Shi et al., “Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity,” The Journal of Biological Chemistry, vol. 285, no. 16, pp. 12169–12180, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. C. Huang, D. Kaigler, K. G. Rice, P. H. Krebsbach, and D. J. Mooney, “Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration,” Journal of Bone and Mineral Research, vol. 20, no. 5, pp. 848–857, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Zhang, V. Madhu, A. S. Dighe, J. N. Irvine Jr., and Q. Cui, “Osteogenic response of human adipose-derived stem cells to BMP-6, VEGF, and combined VEGF plus BMP-6 in vitro,” Growth Factors, vol. 30, no. 5, pp. 333–343, 2012. View at Google Scholar