Vitamin D and Curcumin Mitigate ACLT + MMx-Induced Knee Osteoarthritis by Improving Antioxidant-Related Nrf2/HO-1...

Background: Osteoarthritis (OA) is mainly driven by mechanical damage together with persistent oxidative stress and synovial inflammation, leading to progressive cartilage loss and functional impairment. We evaluated the protective effect of vitamin D and curcumin alone or in combination on OA progression and outcomes in an anterior cruciate ligament transection plus medial meniscectomy (ACLT + MMx) rat model. Methods: OA was induced by ACLT + MMx surgery. Rats were assigned to Sham, OA-control (Control), vitamin D, curcumin, and Vitamin D + Curcumin groups (n = 6/group). Functional outcomes (knee width/swelling and weight-bearing Δ force) and body weight were monitored for 12 weeks. Cartilage damage was assessed by H&E histology and quantitative histomorphometry (cartilage thickness/width) together with degeneration OARSI score assessment. Mechanistic readouts included qPCR for Nrf2 and HO-1, serum oxidative stress markers (MDA, GSSG, CAT), and synovial cytokines (TNF-α, IL-1β, IL-10, MCP-1). Results: OA-control rats showed clear functional deterioration (greater knee swelling and impaired weight bearing), pronounced histological cartilage degeneration, and higher degeneration/OARSI scores. Vitamin D or curcumin treatment improved functional measures, preserved cartilage structure, and reduced cartilage degeneration indices. These benefits were generally strongest with the combined Vitamin D + Curcumin treatment, which showed the greatest overall preservation of cartilage integrity. Treatments were associated with increased synovial Nrf2/HO-1 mRNA expression, improved oxidative stress balance, and a shift toward a less inflammatory synovial cytokine profile. Conclusions: Vitamin D and curcumin, particularly in combination, showed cartilage-protective and functional benefits in ACLT + MMx-induced OA, possibly through coordinated reduction in oxidative stress and synovial inflammation together with increased antioxidant-related Nrf2/HO-1 expression.