Abstract: ob＜x＞jective Knee osteoarthritis (KOA) is a degenerative joint disease characterized by cartilage matrix, cartilage fracture and subchondral bone destruction. The pathogenesis of knee joint KOA is often the change of subchondral bone stress stimulation of articular cartilage, which eventually leads to the destruction of articular cartilage and the occurrence of osteoarthritis, but its specific molecular mechanism is not clear. The purpose of this study is to explore the core genes and key signal pathways in the pathogenesis of osteoarthritis by analyzing the changes of meniscus gene ex＜x＞pression in human KOA patients. Methods First, we download the mRNA ex＜x＞pression dataset GSE45233 from the GEO databa＜x＞se. Then, we divided the tissue samples of patients who underwent meniscectomy because of KOA and meniscectomy because of trauma into KOA group and non-KOA group, and screened the differentially expressed genes (DEGs) from the gene chip data of the two groups. The gene function annotation and signal pathway enrichment analysis of the obtained DEGs were carried out. Protein-protein interaction (PPI) network was constructed, and core module screening and signal pathway enrichment analysis of PPI network were carried out to find out the key signal pathways of core genes related to KOA. Results Signal pathway enrichment shows parathyroid hormone synthesis, secretion and activation, focal adhesion, PPAR signal pathway, chemokine signal pathway and IL-17 signal pathway may be closely related to the pathogenesis of KOA. Ten potential core genes BDNF, SNAP25, CREB1, FPR2, FYN, RTP3, IL2, OPRM1, ADCY8 and ADCY5, which may be involved in KOA were obtained through PPI network, which may be candidate genes for KOA therapy in the future. Conclusion In this study, the key signal pathways that may be related to KOA were identified for the first time, and 10 candidate core genes were screened, which provided a new target and pathway for gene therapy of KOA