Introduction:
Osteoarthritis (OA) is characterized by chronic synovial inflammation, in which synovial macrophages (SMs) play a crucial role. The contribution of JAG1 to macrophage polarization in OA remains unclear.

Material and methods:
Differentially expressed genes (DEGs) were identified by analyzing the GSE64394, GSE55457, and GSE1919 datasets. An in vitro OA model was created. The effects on Notch signaling and macrophage polarization were assessed in IL-1-treated fibroblast-like synoviocytes (FLS) co-cultured with SMs. JAG1 expression was manipulated by siRNA knockdown and overexpression, and downstream effects were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB).

Results:
Eleven overlapping DEGs, including JAG1, IL6, TGFB2, CX3CL1, and MMP1 were identified. Through the construction of cellular models, these genes were found to be potentially associated with inflammation, immune regulation, and extracellular matrix remodeling in OA. Additionally, the OA model was shown to induce polarization of SMs toward the M1 phenotype. In vitro experiments revealed that JAG1 was significantly upregulated in OA samples. JAG1 knockdown in the co-culture model reduced M1 markers (NOS2, PTGS2, CD64, CD86), increased M2 markers (CD206, CD163), and suppressed Notch signaling, while JAG1 overexpression reversed these effects.

Conclusions:
JAG1 promotes the polarization of SMs toward M1 in OA by activating the Notch signaling pathway, providing preliminary evidence that the JAG1/Notch axis may serve as a potential therapeutic target for regulating inflammation and tissue remodeling in OA.