Mst1 inhibition mitigates steroid-induced femoral head osteonecrosis by modulating autophagy in bone microvascular endothelial cells.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition often linked to glucocorticoid use. This research aims to explore the influence of mammalian sterile 20-like kinase 1 (Mst1) on glucocorticoid-induced ONFH, particularly its effects on bone microvascular endothelial cells (BMECs). Methylprednisolone (MPS) was applied to induce BMECs injury in vitro, with or without Mst1 inhibition via shRNA. Significantly improved cell viability, reduced apoptosis, and enhanced angiogenic and migratory capabilities were found after inhibiting Mst1. These protective effects correlated with elevated levels of autophagy-related factors such as Beclin1and LC3, as well as reduced P62 expression, indicating that Mst1 inhibition enhances autophagy. Animal studies using a glucocorticoid-induced ONFH rat model also corroborated these findings. The Mst1 inhibitor XMU-MP-1 treatment improved femoral head condition by enhancing bone microstructure and decreasing apoptosis. Furthermore, XMU-MP-1 treatment upregulated autophagy-related proteins in vivo. These results suggest that Mst1 plays a critical role in glucocorticoid-induced ONFH by modulating autophagy and that Mst1 inhibition may offer a promising therapeutic strategy for this condition.