Optimally dosed nanoceria attenuates osteoarthritic degeneration of joint cartilage and subchondral bone

Osteoarthritis entails excessive ROS generation, severe inflammatory responses, and anatomical destruction of cartilage and subchondral bone. Nanoceria holds antioxidant activity, exerting therapeutic efficacy under high ROS conditions. Here we investigate if the nanoceria properly administered to an osteoarthritic joint would be effective in protecting the cartilage and bone against osteoarthritic degeneration. Three-days post-induction of osteoarthritis in a rat temporomandibular joint, nanoceria (~20 nm) at varying doses (100 ~ 2000 µg/mL) were locally administered once, and tissue samples were analyzed at 10 days post-treatment. The nanoceria-administered groups could preserve the cartilage and subchondral anatomical structure of joint; particularly at 500 µg/mL, the preservation of quantitated hypertrophic layer and cartilage proteoglycan was as high as ~ 80% (vs. ~ 30% in an osteoarthritic group), albeit higher doses gradually shielded the efficacy (~50–60%). The degeneration of subchondral bone was thus significantly prevented by the nanoceria treatment; ~70–80% of intact control with 500 µg/mL vs. ~ 50% in the osteoarthritic group. Moreover, the nanoceria treatment profoundly reduced the degenerative symptoms including cellular apoptosis and the secretion of catabolic proteins (COX2/PGE2) and pro-inflammatory cytokines (IL-1β/TNFα) while boosting regenerative events such as the polarization of M2 macrophages (CD206/163) and the production of anti-inflammatory cytokines (IL-10) and chondrogenic glycoproteins. The excessive ROS generated in the osteoarthritis joint was observed to be effectively scavenged by the nanoceria. Such therapeutic effects of nanoceria witnessed in vivo were further demonstrated in parallel with the in vitro experiments particularly involving the osteoarthritis-mimicking chondrocytes/macrophages co-culture models, where the anti-apoptotic and immunomodulatory roles of nanoceria were revealed to be major molecular mechanisms. The present findings may place the nanoceria a promising nanotherapeutic candidate for the treatment of degenerative joint diseases.