Related Experiment Video
Updated: Aug 24, 2025
Author Spotlight: Developing a Rat Model for Weight-Bearing Intervention to Investigate Osteonecrosis of the Femoral Head
Published on: September 27, 2024
SIRT6 Prevents Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats
Lun Fang1, Gang Zhang2, Yadi Wu1,2
1Institute of Sports Medicine, Shandong First Medical University & Shandong Academy Medical Sciences, Taian, 271016 Shandong Province, China.
Objective:
Glucocorticoid-induced osteonecrosis of the femoral head is one of the most common causes of nontraumatic osteonecrosis of the femoral head, but its exact pathogenesis remains unclear. The aim of this study was to investigate the role of SIRT6 in the maintenance of bone tissue morphology and structure, intravascular lipid metabolism, and its potential molecular mechanism in glucocorticoid-induced osteonecrosis of the femoral head.
Methods:
SIRT6 adenovirus was transfected into GIONFH in rats. The microstructure of rat bone was observed by micro-CT and histological staining, and the expression of bone formation-related proteins and angiogenesis-related factors was determined through western blot and immunohistochemistry. Alkaline phosphatase activity, alizarin red staining, and the expression levels of Runx2 and osteocalcin were used to evaluate the osteogenic potential. And in vitro tube formation assay and immunofluorescence were used to detect the ability of endothelial cell angiogenesis.
Results:
Dexamethasone significantly inhibited osteoblast differentiation, affected bone formation, and destroyed microvessel formation, increased the intracellular Fe2+ and ROS levels and induced the occurrence of ferroptosis. SIRT6 can inhibit ferroptosis and restore the ability of bone formation and angiogenesis.
Conclusion:
SIRT6 can inhibit the occurrence of ferroptosis, reduce the damage of vascular endothelium, and promote osteogenic differentiation, so as to prevent the occurrence of osteonecrosis of the femoral head.
Insights
SIRT6 protein may prevent glucocorticoid-induced osteonecrosis of the femoral head by inhibiting ferroptosis, preserving vascular endothelium, and promoting bone formation and blood vessel growth.
Area of Science:
- Biochemistry
- Orthopedics
- Cell Biology
Background:
- Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common complication with unclear pathogenesis.
- Understanding the molecular mechanisms of GIONFH is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of SIRT6 in maintaining bone structure and lipid metabolism in GIONFH.
- To elucidate the potential molecular mechanism of SIRT6 in GIONFH.
Main Methods:
- SIRT6 adenovirus was used to treat GIONFH in a rat model.
- Micro-CT, histological staining, Western blot, and immunohistochemistry were employed to assess bone microstructure and protein expression.
- Osteogenic potential was evaluated using alkaline phosphatase activity, alizarin red staining, and key protein markers (Runx2, osteocalcin).
- In vitro assays assessed endothelial cell angiogenesis.
Main Results:
- Dexamethasone induced ferroptosis by increasing intracellular Fe2+ and ROS levels, impairing osteoblast differentiation, bone formation, and microvessel integrity.
- SIRT6 expression was found to inhibit ferroptosis and restore bone formation and angiogenesis capabilities.
Conclusions:
- SIRT6 plays a protective role in GIONFH by suppressing ferroptosis.
- SIRT6 mitigates vascular endothelial damage and promotes osteogenic differentiation, offering a potential therapeutic strategy for preventing GIONFH.
