Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model - PubMed (original) (raw)
Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model
A L Bertone et al. J Orthop Res. 2004 Nov.
Free article
Abstract
This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks after surgery in response to percutaneous injection of transgenic adenoviral (Ad) bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector control (Ad-GFP) administered 7 days after surgery compared to untreated osteotomy controls. The amount, composition and biomechanical properties of the healing bone repair tissue were compared among groups and to historical data for intact rabbit ulnae obtained from similar studies at the same institution. Quantitative computed tomography was used to determine area, density and mineral content of the mineralized callus in the harvested ulnae. Maximum torque, torsional stiffness, and energy absorbed to failure were determined at 1.5 degrees /s. Calcified sections of excised ulnae (5 microm) were stained with Goldner's Trichrome and Von Kossa, and evaluated for callus composition, maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of bone formation indicated greater mineralized callus in the ulnae injected with Ad-hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p < 0.002). Quantitative computed tomography confirmed greater bone area and bone mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and 0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque, torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6 treated osteotomy ulnae compared to their respective untreated contralateral osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in the Ad-BMP-6 treated osteotomy ulnae were not different to intact ulnae values at 6 and 8 weeks. These experiments confirm that BMP-6 can be potently osteoinductive in vivo resulting in acceleration of bone repair.
Similar articles
- Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.
Ishihara A, Shields KM, Litsky AS, Mattoon JS, Weisbrode SE, Bartlett JS, Bertone AL. Ishihara A, et al. J Orthop Res. 2008 Jun;26(6):764-71. doi: 10.1002/jor.20585. J Orthop Res. 2008. PMID: 18241059 - Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model.
Bouxsein ML, Turek TJ, Blake CA, D'Augusta D, Li X, Stevens M, Seeherman HJ, Wozney JM. Bouxsein ML, et al. J Bone Joint Surg Am. 2001 Aug;83(8):1219-30. doi: 10.2106/00004623-200108000-00012. J Bone Joint Surg Am. 2001. PMID: 11507131 - rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.
Li RH, Bouxsein ML, Blake CA, D'Augusta D, Kim H, Li XJ, Wozney JM, Seeherman HJ. Li RH, et al. J Orthop Res. 2003 Nov;21(6):997-1004. doi: 10.1016/S0736-0266(03)00082-2. J Orthop Res. 2003. PMID: 14554211 - Recombinant human bone morphogenetic protein-2 delivered in an injectable calcium phosphate paste accelerates osteotomy-site healing in a nonhuman primate model.
Seeherman HJ, Bouxsein M, Kim H, Li R, Li XJ, Aiolova M, Wozney JM. Seeherman HJ, et al. J Bone Joint Surg Am. 2004 Sep;86(9):1961-72. doi: 10.2106/00004623-200409000-00015. J Bone Joint Surg Am. 2004. PMID: 15342759 - The potential of gene therapy for fracture healing in osteoporosis.
Egermann M, Schneider E, Evans CH, Baltzer AW. Egermann M, et al. Osteoporos Int. 2005 Mar;16 Suppl 2:S120-8. doi: 10.1007/s00198-004-1817-9. Epub 2005 Jan 15. Osteoporos Int. 2005. PMID: 15654580 Review.
Cited by
- Percutaneous nonviral delivery of hepatocyte growth factor in an osteotomy gap promotes bone repair in rabbits: a preliminary study.
Matsubara H, Tsuchiya H, Watanabe K, Takeuchi A, Tomita K. Matsubara H, et al. Clin Orthop Relat Res. 2008 Dec;466(12):2962-72. doi: 10.1007/s11999-008-0493-z. Epub 2008 Sep 24. Clin Orthop Relat Res. 2008. PMID: 18813894 Free PMC article. - Orthopedic gene therapy in 2008.
Evans CH, Ghivizzani SC, Robbins PD. Evans CH, et al. Mol Ther. 2009 Feb;17(2):231-44. doi: 10.1038/mt.2008.265. Epub 2008 Dec 9. Mol Ther. 2009. PMID: 19066598 Free PMC article. Review. - Gene delivery to bone.
Evans CH. Evans CH. Adv Drug Deliv Rev. 2012 Sep;64(12):1331-40. doi: 10.1016/j.addr.2012.03.013. Epub 2012 Mar 26. Adv Drug Deliv Rev. 2012. PMID: 22480730 Free PMC article. Review. - Ultrasonic Generation of Pulsatile and Sequential Therapeutic Delivery Profiles from Calcium-Crosslinked Alginate Hydrogels.
Emi T, Michaud K, Orton E, Santilli G, Linh C, O'Connell M, Issa F, Kennedy S. Emi T, et al. Molecules. 2019 Mar 16;24(6):1048. doi: 10.3390/molecules24061048. Molecules. 2019. PMID: 30884862 Free PMC article. - The challenges of promoting osteogenesis in segmental bone defects and osteoporosis.
Ball AN, Donahue SW, Wojda SJ, McIlwraith CW, Kawcak CE, Ehrhart N, Goodrich LR. Ball AN, et al. J Orthop Res. 2018 Jun;36(6):1559-1572. doi: 10.1002/jor.23845. Epub 2018 Mar 6. J Orthop Res. 2018. PMID: 29280510 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources