Müller F J, Setton L A, Manicourt D H, Mow V C, Howell D S, Pita J C
Veterans Administration Medical Center, Miami, Florida.
J Orthop Res. 1994 Jul;12(4):498-508. doi: 10.1002/jor.1100120406.
Two models involving altered joint loading were compared with regard to their effects on the biochemical composition and proteoglycan aggregate structure of articular cartilage. Disuse atrophy was created in greyhound dogs by nonrigid immobilization of the right knee in 90 degrees of flexion, and joint instability was created by transection of the anterior cruciate ligament. Similarities and differences between the two experimental groups at two different time periods were examined to investigate why joint instability induces progressive and irreversible changes to the articular cartilage, whereas joint disuse induces changes that may be reversible when the joint is remobilized. The following studies were performed on the cartilage from all experimental and control groups: (a) compositional analyses to determine water, uronate, and hydroxyproline contents; (b) high performance liquid chromatography for detection of hyaluronan and chondroitin sulfates; and (c) centrifugation analyses of nondissociatively extracted and purified proteoglycans to isolate and quantify the populations of monomers and slow and fast-sedimenting families of aggregates. In general, all cartilage was found to have a decreased ratio of proteoglycan to collagen after 4 weeks of disuse, and this ratio returned to control values at 8 weeks. In contrast, cartilage had an elevated ratio of proteoglycan to collagen as well as increased hydration at 12 weeks after transection of the anterior cruciate ligament. The most striking contrast between the two models was the finding of an approximately 80% decrease in the content of hyaluronan at both time periods after transection of the anterior cruciate ligament, with no evidence of a change after disuse. The results of centrifugation analyses indicated a significant decrease in the quantity of proteoglycan aggregates in both models. However, this decrease was associated primarily with a loss of slow-sedimenting aggregates after disuse and a loss of both slow and fast-sedimenting aggregates after transection of the anterior cruciate ligament. Furthermore, the population of fast-sedimenting aggregates was depleted to a greater extent than that of the slow-sedimenting aggregates. The preservation of fast-sedimenting aggregates as well as hyaluronan after periods of joint disuse but not joint instability suggests a possible mechanism for the reversibility of cartilage changes. Although the proteoglycan aggregates were depleted after disuse atrophy, it is possible that an aggregate-depleted matrix could recover when normal proteoglycan synthesis is resumed. In contrast, although synthesis may be maintained or elevated after transection of the anterior cruciate ligament, the matrix may not be repopulated with aggregates because there is an insufficient amount of hyaluronan.
比较了两种涉及关节负荷改变的模型对关节软骨生化组成和蛋白聚糖聚集体结构的影响。通过将灵缇犬的右膝非刚性固定在90度屈曲位造成废用性萎缩，通过切断前交叉韧带造成关节不稳定。研究了两个实验组在两个不同时间段的异同，以探讨为什么关节不稳定会导致关节软骨发生进行性和不可逆的变化，而关节废用引起的变化在关节重新活动时可能是可逆的。对所有实验组和对照组的软骨进行了以下研究：(a)成分分析以确定水、糖醛酸和羟脯氨酸含量；(b)高效液相色谱法检测透明质酸和硫酸软骨素；(c)对非解离提取和纯化的蛋白聚糖进行离心分析，以分离和定量单体以及慢速和快速沉降聚集体家族的数量。一般来说，所有软骨在废用4周后蛋白聚糖与胶原蛋白的比例降低，8周时该比例恢复到对照值。相比之下，在前交叉韧带切断12周后，软骨的蛋白聚糖与胶原蛋白比例升高，水合作用增加。两种模型最显著的对比是，在前交叉韧带切断后的两个时间段，透明质酸含量均下降了约80%，而废用后没有变化的迹象。离心分析结果表明，两种模型中蛋白聚糖聚集体的数量均显著减少。然而，这种减少主要与废用后慢速沉降聚集体的丢失以及前交叉韧带切断后慢速和快速沉降聚集体的丢失有关。此外，快速沉降聚集体的数量比慢速沉降聚集体的数量减少得更多。关节废用而非关节不稳定后快速沉降聚集体以及透明质酸的保留提示了软骨变化可逆性的一种可能机制。虽然废用性萎缩后蛋白聚糖聚集体减少，但当正常蛋白聚糖合成恢复时，聚集体减少的基质有可能恢复。相比之下，虽然在前交叉韧带切断后合成可能维持或升高，但由于透明质酸量不足，基质可能无法重新填充聚集体。
