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

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

  • Biochem Pharmacol. 2025 Sep:239:117081. doi: 10.1016/j.bcp.2025.117081.
Yaqi Zhang 1,  Tongmeng Jiang 2,  Bo Li 3,  Guoyuan Sun 1,  Yake Wang 1,  Yankun Jiang 1,  Pengbing Hua 4,  Xiaohong Mu 5,  Weiguo Wang 6,  Qidong Zhang 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, China-Japan Friendship Hospital, Beijing 100029, China.
  • 2 Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou 571199, China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China. Electronic address: jiangtongmeng@muhn.edu.cn.
  • 3 The Department of Orthopedics, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • 4 Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital, Hainan Medical University, Haikou 571199, China; Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China.
  • 5 Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China. Electronic address: muxiaohong2006@126.com.
  • 6 Department of Orthopedics, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: jointwwg@163.com.
  • 7 Department of Orthopedics, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address: zhangqidong1982@sina.com.
PMID: 40562116 DOI: 10.1016/j.bcp.2025.117081
Abstract

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.

Keywords

Autophagy; Bone microvascular endothelial cells (BMECs); Glucocorticoid; Mst1; Osteonecrosis of the femoral head (ONFH).

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