Osteoarthritis (OA) is the most common form of arthritis and is caused by the breakdown of joint cartilage. The present study aimed to investigate an effective method for the treatment of OA. It was demonstrated that, compared with other patients, patients with OA exhibited lower mRNA expression levels of SMAD family member 2 (SMAD2). MicroRNA (miR)‑486‑5p was predicted to bind with SMAD2, which was verified by dual‑luciferase reporter assay. Compared withcontrol patients who had no known history of OA or rheumatoid arthritis, patients with OA exhibited higher miR‑486‑5p expression level. Treatment with miR‑486‑5p mimics inhibited proliferation and migration of CHON‑001 human chondrocytes, and also inhibited the expression levels of type II collagen and aggrecan. However, treatment with a miR‑486‑5p inhibitor promoted proliferation and migration, and the expression of type II collagen and aggrecan. Short interfering RNA‑directed silencing of SMAD2 reversed the upregulated proliferation and migration and the expression level of type II collagen and aggrecan induced by the miR‑486‑5p inhibitor. In conclusion, the results of the present study indicated that miR‑486‑5p was upregulated in OA and may inhibit chondrocyte proliferation and migration by suppressing SMAD2.