Context: Osteoarthritis (OA) is a high-incidence, chronic condition, with an extremely high prevalence among older adults. OA seriously compromises the normal living of OA patients, and it's imperative to find a novel therapy as soon as possible to improve their prognosis and life quality.

Objective: The study intended to investigate the therapeutic effects of Curcumin (Cur) on OA and to explore its preliminary mechanism of action, with the aim of offering more accurate guidance for use of OA therapy.

Design: The research team designed a prospective non-randomized controlled trial.

Setting: The study took place in the Department of Orthopedics at Sir Run Run Hospital at Nanjing Medical University in Nanjing, China.

Participants: Participants were 107 OA patients treated at the hospital between March 2019 and January 2020.

Intervention: Participants were divided into two groups, 51 in the Cur group and 56 in the ibuprofen group.

Outcome measures: The clinical efficacy and safety of the two groups were observed. In addition, the research team performed in-vitro studies. Chondrocytes HC-a and C28/I2 were purchased to evaluate the intracellular inflammatory response and apoptosis rate under the intervention of Cur and Wnt/β-catenin pathway inhibitors.

Results: No significant differences existed in the clinical-efficacy rate between the two groups (P > .05), but the Cur group show higher improvements in safety, joint mobility, and inhibition of inflammation (P < .05). In-vitro experiments showed that Cur inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/β-catenin inhibitor did the opposite (P < .05).

Conclusions: Cur can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/β-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes.