| Osteoarthritis (OA) is a chronic degenerative disease characterized by joint cartilage degradation, synovial inflammation, and abnormal bone remodeling. Traditional treatments primarily focus on symptom relief and are often unable to reverse the pathological progression. In recent years, therapeutic strategies targeting cytokines and signaling pathways have emerged as a research focus, offering new perspectives for disease-modifying treatments in OA. This review summarizes the regulatory mechanisms of key cytokines (such as IL-1β, TNF-α) and signaling pathways (such as NF-κB, Wnt, JAK/STAT) involved in the pathogenesis of OA, and explores their roles in promoting catabolic processes and inhibiting anabolic processes, thereby exacerbating OA progression. Furthermore, it analyzes potential strategies for targeted therapy, including cytokine antagonists (such as IL-1Ra), small molecule inhibitors of signaling pathways (such as TGF-β kinase inhibitors), and the advancements and clinical translation challenges of gene therapy. Finally, the review discusses the future prospects of multi-targeted interventions, nanocarrier delivery technologies, and personalized treatment in the field of OA, providing a theoretical basis for the development of efficient and low-toxicity targeted drugs. |