Aim or purpose: To explore the molecular mechanism by which HDAC6 regulates the cytoskeleton through post-translational modifications, thus leading to OA-like changes in the phenotype of chondrocytes. Materials and methods: 1. Establish an OA animal model, identify the expression of HDAC6, and conduct sequencing analysis of the OA model to explore its correlation with the cytoskeleton.2.Construct an in vitro model of inflamed chondrocytes to verify the expression of HDAC6 in these inflamed chondrocytes. Observe the changes in cell phenotypes by overexpressing and knocking down HDAC6. 3.Verify the mechanism of interaction between HDAC6 and acetylated cytoskeletal proteins through protein-protein interactions. Results: 1.In the OA animal model, the expression of HDAC6 is increased, and sequencing results show a close correlation with the cytoskeleton. 2.In the in vitro model of inflamed chondrocytes, the high expression of HDAC6 in OA is verified. When HDAC6 is overexpressed, an OA chondrocyte phenotype appears, and when HDAC6 is knocked down, the OA cell phenotype shows a certain degree of restoration. Conclusions: HDAC6 plays a crucial role in the process of cartilage degeneration in OA. It may regulate the cytoskeleton through post-translational modifications, prompting OA-like changes in the phenotype of chondrocytes, which provides a new direction for a deeper understanding of the pathogenesis of OA.