Pennock Andrew T, Robertson Catherine M, Emmerson Bryan C, Harwood Frederick L, Amiel David
University of California, San Diego, CA 92093-0630, USA.
Arthritis Rheum. 2007 May;56(5):1529-36. doi: 10.1002/art.22523.
To determine expression patterns of apoptotic and matrix-degrading genes during aging and development of osteoarthritis (OA), using a rabbit model of induced OA.
Six mature and 6 aged rabbits underwent anterior cruciate ligament transection and were killed 4 and 8 weeks after surgery, respectively, to create early-grade and advanced-grade OA. RNA from articular cartilage and menisci was examined for expression of the genes caspase 8, Fas, Fas ligand, p53, aggrecanase, matrix metalloproteinase 1 (MMP-1), and MMP-3. A second cohort of animals that had undergone no intervention in the joint was also killed. Parametric data were analyzed with analysis of variance and Student's t-tests, while nonparametric data were assessed with the Mann-Whitney U test.
Expression levels of Fas, caspase 8, FasL, and MMP-1 were significantly higher (>100%) in aged cartilage compared with mature cartilage (P < 0.05). After induction of OA, expression of apoptotic genes in aged rabbits remained high, while significant up-regulation of Fas and caspase 8 (nearly 150% increase) was observed in mature rabbits (P < 0.05). No significant up-regulation of these genes was observed in the menisci of aged or mature rabbits prior to or after induction of OA. Development of OA occurred more rapidly in aged cartilage compared with mature cartilage (P < 0.05).
Differential expression of apoptotic and matrix-degrading genes occurs in aged compared with mature cartilage, both at baseline and during development of OA. This may be responsible for faster degradation of aged cartilage and its predisposition for developing OA.
利用兔诱导性骨关节炎（OA）模型，确定凋亡基因和基质降解基因在OA衰老和发展过程中的表达模式。
6只成年兔和6只老年兔接受前交叉韧带切断术，分别在术后4周和8周处死，以建立早期和晚期OA模型。检测关节软骨和半月板RNA中半胱天冬酶8、Fas、Fas配体、p53、聚集蛋白聚糖酶、基质金属蛋白酶1（MMP-1）和MMP-3基因的表达。另一组未对关节进行干预的动物也被处死。参数数据采用方差分析和学生t检验进行分析，非参数数据采用曼-惠特尼U检验进行评估。
与成熟软骨相比，老年软骨中Fas、半胱天冬酶8、FasL和MMP-1的表达水平显著更高（>100%）（P<0.05）。诱导OA后，老年兔凋亡基因的表达仍然很高，而在成年兔中观察到Fas和半胱天冬酶8显著上调（增加近150%）（P<0.05）。在诱导OA之前或之后，老年或成年兔半月板中这些基因均未观察到显著上调。与成熟软骨相比，老年软骨中OA的发展更快（P<0.05）。
与成熟软骨相比，老年软骨在基线和OA发展过程中凋亡基因和基质降解基因存在差异表达。这可能是老年软骨更快降解及其易患OA的原因。
