On the one hand, previous studies have shown that the Akt signaling pathway of chondrocytes is downregulated when exposed to IL-1b and TNF-α, leading to cell apoptosis,35,36 while activating the Akt signaling pathway by FGF18 can alleviate OA progress.36 Our study found that blood downregulates the Akt signaling pathway while activation of the pathway alleviates blood-induced cartilage damage both in vivo and in vitro, which is the first study to confirm the role of Akt in hemarthrosis. Here, TNF is linked to hemarthrosis.