GDF11 alleviates glucocorticoid-induced osteonecrosis of the femoral head by regulating angiogenesis via the PI3K-AKT-eNOS pathway.

Glucocorticoid-induced osteonecrosis of the femoral head is a joint dysfunction disease. Impaired local angiogenesis and reduced perfusion are early pathological features of glucocorticoid-induced osteonecrosis of the femoral head, resulting from vascular endothelial cell damage and suppressed angiogenesis caused by prolonged glucocorticoid exposure. This study focuses on the role of angiogenesis in glucocorticoid-induced osteonecrosis of the femoral head, particularly the potential of GDF11 in promoting angiogenesis. Our findings indicate that GDF11 expression diminished in patients with osteonecrosis of the femoral head compared to those with femoral neck fractures. We establish a male Sprague-Dawley rat model of glucocorticoid-induced osteonecrosis of the femoral head and utilize human umbilical vein endothelial cells to explore the role of GDF11 on osteogenesis and angiogenesis. A series of in vivo and in vitro experiments are conducted, the result shows that GDF11 could reverse the damaged angiogenic and osteogenic ability caused by methylprednisolone. We perform RNA sequencing in human umbilical vein endothelial cells and reveal that GDF11 promotes the expression of angiogenic factors and migration of endothelial cells through activating the PI3K/AKT/eNOS pathway, thereby promoting angiogenesis. Our study clarifies the role and mechanism of GDF11 in regulating local angiogenesis in glucocorticoid-induced osteonecrosis of the femoral head.