Laurent Didier, O'Byrne Elizabeth, Wasvary James, Pellas Theodore C
Novartis Institutes for Biomedical Research, Inc., 250 Massachusetts Avenue, Cambridge, MA 02139, USA.
Skeletal Radiol. 2006 Aug;35(8):555-64. doi: 10.1007/s00256-006-0133-1. Epub 2006 Apr 26.
To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).
Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k(m) for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network. Local changes in cartilage fixed charge density, i.e., where PGs are depleted, were derived from T(1) relaxation maps as obtained after an infusion of Gd(DTPA)(2-), a paramagnetic agent.
In the goat model, the MT rate constant k(m) was significantly higher at 2 weeks post surgery, a possible sign of cartilage swelling, then decreased below baseline values, most likely indicative of disruption in the collagen framework. Meanwhile, post-Gd(DTPA)(2-) MRI acquisition indicated a significant and sustained loss of PGs. The rabbit model produced milder lesions. Although the difference was non-significant, k(m) steadily decreased in response to the surgical insult while kinetics of Gd(DTPA)(2-) uptake, after reaching a peak level at 6 weeks, were back to normal values after 12 weeks.
In the goat model, joint instability and cartilage damage was a permanent trigger for cartilage degeneration producing MRI changes. However, biomechanical stress due to partial medial meniscectomy in knees of mature rabbits produced only mild, focal lesions and PG depletion that was partially reversible. This proof-of-concept study identified MT and T(1) parameters as useful surrogate markers in animal models of osteoarthritis.
在两种骨关节炎手术模型（山羊：半月板横断和软骨切开；兔子：内侧半月板切除术）中，研究关节软骨大分子组成的体内时程变化。
在两种模型中，分别通过磁化转移（MT）和对比增强MRI评估胶原蛋白完整性和蛋白聚糖（PG）含量。确定了本体水与结合在胶原蛋白上的水之间交换过程的MT率k(m)，作为胶原蛋白网络的标志物。软骨固定电荷密度的局部变化，即PG耗竭的部位，由注入顺磁性剂钆喷酸葡胺（Gd(DTPA)₂⁻）后获得的T₁弛豫图得出。
在山羊模型中，术后2周MT率常数k(m)显著更高，这可能是软骨肿胀的迹象，随后降至基线值以下，很可能表明胶原蛋白框架遭到破坏。同时，钆喷酸葡胺（Gd(DTPA)₂⁻）增强MRI采集显示PG显著且持续丢失。兔子模型产生的损伤较轻。尽管差异不显著，但k(m)因手术损伤而稳步下降，而钆喷酸葡胺（Gd(DTPA)₂⁻）摄取动力学在6周达到峰值水平后，12周后恢复到正常值。
在山羊模型中，关节不稳定和软骨损伤是导致软骨退变并产生MRI变化的永久性触发因素。然而，成年兔子膝关节内侧半月板部分切除所产生 的生物力学应力仅产生轻度、局灶性损伤以及部分可逆的PG耗竭。这项概念验证研究确定MT和T₁参数是骨关节炎动物模型中有用的替代标志物。
