Role of apoptotic and matrix-degrading genes in articular cartilage and meniscus of mature and aged rabbits during development of osteoarthritis.

Objective: To determine expression patterns of apoptotic and matrix-degrading genes during aging and development of osteoarthritis (OA), using a rabbit model of induced OA.

Methods: 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.

Results: 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).

Conclusion: 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.