• A novel combined D-galactose injection and anterior cruciate ligament transection (ACLT) method successfully establishes a stable aging-related knee osteoarthritis model in SD rats.
• The combined model exhibits more severe cartilage degeneration, synovial inflammation, and chondrocyte senescence compared to either D-galactose or ACLT alone.
• The model shows increased chondrocyte cell cycle arrest at G0/G1 phase, elevated senescence-associated β-galactosidase activity, and DNA damage response (γ-H2AX), indicating cellular senescence.
• This model better mimics the pathological features of aging-related knee osteoarthritis and provides a valuable tool for studying the mechanisms and therapeutic interventions of the disease.