Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Osteoarthritis Cartilage. 2011 Aug;19(8):1066-75. doi: 10.1016/j.joca.2011.05.007. Epub 2011 Jun 2.
To evaluate healing of surgically created large osteochondral defects in a weight-bearing femoral condyle in response to delayed percutaneous direct injection of adenoviral (Ad) vectors containing coding regions for either human bone morphogenetic proteins 2 (BMP-2) or -6.
Four 13mm diameter and 7mm depth circular osteochondral defects were drilled, 1/femoral condyle (n=20 defects in five ponies). At 2 weeks, Ad-BMP-2, Ad-BMP-6, Ad-green fluorescent protein (GFP), or saline was percutaneously injected into the central drill hole of the defect. Quantitative magnetic resonance imaging (qMRI) and computed tomography (CT) were serially performed at 12, 24, and 52 weeks. At 12 (one pony) or 52 weeks, histomorphometry and microtomographic analyses were performed to assess subchondral bone and cartilage repair tissue quality.
Direct delivery of Ad-BMP-6 demonstrated delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and histologic evidence of greater Glycosaminoglycan (GAG) content in repair tissue at 12 weeks, while Ad-BMP-2 had greater non-mineral cartilage at the surface at 52 weeks (p<0.04). Ad-BMP-2 demonstrated greater CT subchondral bone mineral density (BMD) by 12 weeks and both Ad-BMP-2 and -6 had greater subchondral BMD at 52 weeks (p<0.05). Despite earlier (Ad-BMP-6) and more persistent (Ad-BMP-2) chondral tissue and greater subchondral bone density (Ad-BMP-2 and -6), the tissue within the large weight-bearing defects at 52 weeks was suboptimal in all groups due to poor quality repair cartilage, central fibrocartilage retention, and central bone cavitation. Delivery of either BMP by this method had greater frequency of subchondral bone cystic formation (p<0.05).
Delivery of Ad-BMP-2 or Ad-BMP-6 via direct injection supported cartilage and subchondral bone regeneration but was insufficient to provide long-term quality osteochondral repair.
评估经皮直接注射携带编码人骨形态发生蛋白 2（BMP-2）或 -6 的腺病毒（Ad）载体对负重股骨髁中大骨软骨缺损愈合的影响。
在 2 周时，经皮向每个骨软骨缺损的中央钻孔中注射 Ad-BMP-2、Ad-BMP-6、Ad-绿色荧光蛋白（GFP）或生理盐水。在 12、24 和 52 周时，连续进行定量磁共振成像（qMRI）和计算机断层扫描（CT）。在 12 周（一匹马）或 52 周时，进行组织形态计量学和微断层分析，以评估软骨下骨和软骨修复组织的质量。
直接递送 Ad-BMP-6 在 12 周时显示出延迟钆增强 MRI 软骨成像（dGEMRIC）和修复组织中糖胺聚糖（GAG）含量增加的组织学证据，而 Ad-BMP-2 在 52 周时在表面具有更大的非矿化软骨（p<0.04）。Ad-BMP-2 在 12 周时显示出更大的 CT 软骨下骨骨密度（BMD），并且 Ad-BMP-2 和 -6 在 52 周时均显示出更大的软骨下 BMD（p<0.05）。尽管 Ad-BMP-6 更早（Ad-BMP-6）和更持久（Ad-BMP-2）的软骨组织和更大的软骨下骨密度（Ad-BMP-2 和 -6），但在 52 周时，所有组的大负重缺损内的组织由于修复软骨质量差、中央纤维软骨保留和中央骨空洞形成而不理想。通过这种方法递送的任何一种 BMP 都更频繁地导致软骨下骨囊性形成（p<0.05）。
经皮直接注射 Ad-BMP-2 或 Ad-BMP-6 可支持软骨和软骨下骨再生，但不足以提供长期高质量的骨软骨修复。
