Targeting SOD3-Mediated Oxidative Stress with Betulonic Acid Protects Against Steroid-Induced Femoral Head Necrosis.

Authors

Qi Chen, Yangquan Hao, Wenxing Yu, Yuheng Yan, Jiadong Chen, Chao Lu

Published in

Drug design, development and therapy. Volume 20. Pages 594601. Epub Sep 02, 2026.

Abstract

Steroid-induced osteonecrosis of the femoral head (SONFH) is a devastating complication of glucocorticoid therapy, fundamentally driven by oxidative stress. Although Betulonic acid (Ba), a natural pentacyclic triterpenoid, exhibits potent antioxidant properties, its therapeutic efficacy in SONFH remains unknown. This study investigates the protective effects of Ba against SONFH, specifically focusing on its capacity to restore extracellular redox homeostasis via superoxide dismutase 3 (SOD3).
A rat SONFH model was induced using lipopolysaccharide and methylprednisolone, followed by Ba treatment. Femoral head architecture was evaluated via Micro-CT and histopathology. In vitro, MC3T3-E1 osteoblasts were treated with dexamethasone (Dex) and Ba. Cell viability, intracellular ROS, and superoxide anion levels were assessed. RNA sequencing identified differentially expressed genes, and the mechanism was validated using Sod3 siRNA knockdown and lentiviral overexpression assays.
Ba administration significantly attenuated osteonecrosis in vivo, preserving bone mineral density (p < 0.01) and preventing trabecular collapse. In vitro, Ba mitigated Dex-induced osteoblast cytotoxicity and excessive reactive oxygen species (ROS) accumulation. Transcriptomic profiling revealed that Ba predominantly restored antioxidant pathways, notably reversing the Dex-induced downregulation of Sod3. Crucially, targeted functional assays demonstrated that SOD3 is an important mediator of this protection: Sod3 silencing abolished Ba's therapeutic efficacy, whereas Sod3 overexpression independently conferred profound resistance to oxidative injury.
Ba effectively ameliorates glucocorticoid-induced osteonecrosis by reconstituting the critical extracellular antioxidant barrier, a process closely associated with SOD3 upregulation. These findings establish Ba as a promising natural therapeutic agent and highlight extracellular redox modulation as a novel strategy for SONFH management.

PMID:
42703376
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.