Design of the experiment. Our in vitro knee tissue co-culture model was built from the three main tissue types (i.e., synovial membrane, subchondral bone, and hyaline cartilage), which play roles in the pathogenesis of OA. The structure of the model allows similar communication pathways as it happens in vitro. (A) After building the model, tissues were stimulated by IL-1β for 2 days or cultured without IL-1β as a negative control. Medium was exchanged in the IL-1β-stimulated cultures and tissues were treated with 10% hyperacute serum for 5 days. We used human serum albumin with a matched albumin content as a negative control for 5 days (B).