[Shaoyangzhugu Formula regulates p19(Arf)-p53-p21(Cip1) signaling pathway to ameliorate cartilage degeneration in aged cynomolgus monkeys with knee osteoarthritis].

OBJECTIVE: To study the effect of Shaoyangzhugu (SYZG) Formula (a formula consisting of 9 traditional Chinese drugs) in delaying the degeneration of articular cartilage and the role p19(Arf)-p53-p21(Cip1) signaling pathway in mediating this effect. METHOD: Thirteen aged cynomolgus monkeys with degenerative knee joints were selected based on X-ray findings, and one of them was randomly selected for pathological observation. The other monkeys were randomized equally into SYZG Formula group (treated with SYZG decoction), ammonia moxime group and saline group. All the monkeys were sacrificed after 8 weeks of treatment with intragastric administration of the drugs or saline. The pathology in the knee joint articular cartilage was observed and the mRNA and protein expressions of p19(Arf), p53, and p21(Cip1) in the articular cartilage were detected using RT-qPCR and Western blotting. RESULTS: The pathological findings of the articular cartilage in old cynomolgus monkeys were consistent with the characteristics of knee osteoarthritis (KOA). Mankin scores of the cynomolgus monkeys were 7.38∓0.52 in SYZG Formula group, 7.88∓0.83 in ammonia moxime group, and 8.38∓0.74 in saline group, showing a significant difference between SYZG Formula group and saline group (P<0.05). The expressions of p19(Arf), p53, and p21(Cip1) were the lowest in SYZG Formula group and the highest in saline group with significant differences among the 3 groups (P<0.05). CONCLUSION: SYZG Formula can delay chondrocyte senescence by regulating p19(Arf)-p53-p21(Cip1) signaling pathway to delay articular cartilage degeneration in aged cynomolgus monkeys.