| Osteoarthritis (OA) is a clinically prevalent degenerative joint disease. It is closely associated with abnormal bone metabolism. Copper is an essential trace element for maintaining the function of the bone and joint tissues. After dietary, copper is absorbed in the small intestine/duodenum. It is distributed to cartilage and bone tissues via copper transporter 1 (CTR1). Copper regulates the differentiation of mesenchymal stem cells into chondrocytes, promotes lysyl oxidase (LOX)-mediated collagen cross-linking, and inhibits the M1 polarization of synovial macrophages. However, copper metabolic disorders (deficiency or overload) may drive the progression of OA. Copper deficiency, which may result from long-term total parenteral nutrition, Menkes disease, or other causes, disrupts cartilage collagen by reducing LOX activity, induces the accumulation of reactive oxygen species (ROS) through inhibiting superoxide dismutase 1 (SOD1), and promotes inflammation via activating the NF-κB pathway. On the other hand, copper overload (arising from environmental exposure, Wilson disease, etc.) induces chondrocyte cuproptosis through the Haber-Weiss reaction, increases the activity of matrix metalloproteinase-13 (MMP-13) by inhibiting zinc absorption, and exacerbates tissue damage by activating the NLRP3 inflammasome. Additionally, copper-based materials (e.g., Cu-BGC, Au24Cu1-DMSNs-PEG) have shown potential in OA intervention. Nevertheless, current research has obvious limitations, including that the dynamic monitoring technology for copper metabolism is not yet mature, making it difficult to accurately track the absorption, transport and tissue distribution of copper ions in vivo. Meanwhile, there is a lack of specific copper metabolism-related animal models that highly match the pathological characteristics of clinical OA, which restricts the in-depth verification of the association mechanism between copper metabolic disorders and OA as well as the translational research of intervention strategies. |