Bertone A L, Pittman D D, Bouxsein M L, Li J, Clancy B, Seeherman H J
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 601 Tharp St., The Ohio State University, Columbus 43210, USA.
J Orthop Res. 2004 Nov;22(6):1261-70. doi: 10.1016/j.orthres.2004.03.014.
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.
本研究评估了兔双侧尺骨截骨术后6周和8周的愈合情况，这些兔子在术后7天接受了经皮注射转基因腺病毒（Ad）骨形态发生蛋白-6（BMP-6）载体或绿色荧光蛋白载体对照（Ad-GFP），并与未治疗的截骨对照进行比较。比较了各组愈合骨修复组织的数量、组成和生物力学特性，并与同一机构类似研究中获得的完整兔尺骨的历史数据进行比较。使用定量计算机断层扫描来确定收获的尺骨中矿化骨痂的面积、密度和矿物质含量。在1.5度/秒的速度下测定最大扭矩、扭转刚度和破坏时吸收的能量。切除的尺骨（5微米）钙化切片用Goldner三色染色法和Von Kossa染色法染色，并评估骨痂组成、成熟度、皮质连续性和截骨桥接情况。骨形成的影像学评估表明，与未治疗的截骨尺骨（p < 0.006）和Ad-GFP治疗的截骨尺骨（p < 0.002）相比，注射Ad-hBMP-6的尺骨在治疗后1周（术后2周）就有更多的矿化骨痂。定量计算机断层扫描证实，与未治疗的截骨尺骨（p < 0.001）和Ad-GFP治疗的截骨尺骨（p < 0.01）相比，Ad-BMP-6治疗的截骨在6周时截骨处的骨面积和骨矿物质含量更大。Ad-BMP-6治疗的截骨尺骨在6周时的扭转强度（p < 0.001和0.003）和刚度（p < 0.004和0.003）分别比未治疗的截骨尺骨或Ad-GFP治疗的截骨尺骨更强。与各自未治疗的对侧截骨尺骨相比，Ad-BMP-6治疗的截骨尺骨在8周时的最大扭矩、扭转刚度和破坏时吸收的能量更大[p < 0.03]。Ad-BMP-6治疗的截骨尺骨在6周和8周时的最大扭矩和扭转刚度与完整尺骨的值没有差异。这些实验证实，BMP-6在体内具有强大的骨诱导作用，可加速骨修复。
