Crebanine mitigates glucocorticoid‐induced osteonecrosis of the femoral head by restoring bone remodelling homeostasis via attenuating oxidative stress

Author:

Dong Shankun1,Ge Jianxun1,Meng Qi1,Yuan Tao1,Wang Yi23,Li Yi23,Lu Qizhen23,Song Wenao4,Li Ziqing23,Sun Shui123ORCID

Affiliation:

1. Department of Joint Surgery Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University Jinan Shandong China

2. Department of Joint Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong China

3. Orthopaedic Research Laboratory, Medical Science and Technology Innovation Center Shandong First Medical University and Shandong Academy of Medical Sciences Jinan Shandong China

4. Department of Clinical Laboratory Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University Jinan Shandong China

Abstract

AbstractThe onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long‐term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti‐inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)‐stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX‐induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro‐CT and histological data, which also showed that CN attenuated MPS‐induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs‐induced ONFH.

Funder

Natural Science Foundation of Shandong Province

National Natural Science Foundation of China

Publisher

Wiley

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