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Updated: Apr 27, 2026
Author Spotlight: Developing a Rat Model for Weight-Bearing Intervention to Investigate Osteonecrosis of the Femoral Head
Published on: September 27, 2024
Preventive effects of siRNA targeting PPARγ gene on steroid-induced osteonecrosis in rabbits
Jinfeng Li1, Yuebai Li, Yisheng Wang
1Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhengzhou University , Zhengzhou , China .
Unlabelled:
PURPOSES/AIM: Glucocorticoid steroids can induce expression of PPARγ gene and enhance adipogenesis by bone marrow mesenchymal stem cells (BMSCs), which may result in osteonecrosis of the femoral head. Currently, there are no medications available to prevent steroid-induced osteonecrosis. We hypothesized that siRNA targeting PPARγ gene may prevent steroid-induced adipogenesis and osteonecrosis in rabbit. The purpose of this study was to evaluate the preventive effects of siRNA targeting PPARγ gene on steroid-induced adipogenesis and osteonecrosis.
Methods:
Forty-eight healthy New Zealand rabbits were randomized into four groups with Group M treated with dexamethasone only, Group S with dexamethasone and a recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene, Group Con with dexamethasone and a vector carrying irrelative sequence, and Group N with no treatment serving as control. Expressions of the PPARγ, osteocalcin and Runx2 genes, as well as histopathologic changes were evaluated.
Results:
The levels of PPARγ gene expression were decreased while the levels of osteocalcin and Runx2 gene expression were increased in rabbits treated with dexamethasone and recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene (Group S), compared to rabbits treated either with dexamethasone alone (Group M) or with both dexamethasone and a vector carrying irrelative sequence (Group Con). The marrow necrosis, adipocyte hypertrophy and proliferation, diminished hematopoiesis, thinner and sparse trabeculae, and increased empty osteocyte lacunae in the femoral head were observed in Group M and Group Con rabbits. However, no such changes were seen in Group S rabbits that were treated with dexamethasone and a recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene.
Conclusion:
siRNA targeting PPARγ gene can inhibit adipogenic differentiation of BMSCs and prevent steroid-induced osteonecrosis in rabbit. The inhibition of bone-marrow adipogenesis and concomitant enhancement of osteogenesis with RNAi may provide a novel approach to the prevention of steroid-induced osteonecrosis.
Insights
Small interfering RNA (siRNA) targeting the PPARγ gene effectively prevented steroid-induced osteonecrosis in rabbits by inhibiting bone marrow mesenchymal stem cell adipogenesis. This RNA interference approach offers a promising new strategy for preventing this condition.
Area of Science:
- Biomedical Science
- Molecular Biology
- Regenerative Medicine
Background:
- Glucocorticoids induce PPARγ gene expression and adipogenesis in bone marrow mesenchymal stem cells (BMSCs).
- This process can lead to osteonecrosis of the femoral head, a condition with no current preventative medications.
- This study investigates a potential preventative strategy targeting PPARγ.
Purpose of the Study:
- To evaluate the preventive effects of siRNA targeting the PPARγ gene on steroid-induced adipogenesis and osteonecrosis in a rabbit model.
Main Methods:
- Forty-eight rabbits were randomized into four groups: dexamethasone only, dexamethasone with PPARγ siRNA, dexamethasone with control vector, and no treatment.
- Gene expression of PPARγ, osteocalcin, and Runx2 was analyzed.
- Histopathological changes in the femoral head were assessed.
Main Results:
- Rabbits treated with dexamethasone and PPARγ siRNA showed decreased PPARγ expression and increased osteocalcin and Runx2 expression.
- Dexamethasone-treated groups without siRNA exhibited femoral head necrosis, adipocyte changes, and impaired hematopoiesis.
- These adverse histopathological changes were absent in the group treated with PPARγ siRNA.
Conclusions:
- siRNA targeting the PPARγ gene effectively inhibits BMSC adipogenic differentiation.
- This inhibition prevents steroid-induced osteonecrosis in rabbits.
- Targeting bone marrow adipogenesis with RNAi presents a novel preventative approach for steroid-induced osteonecrosis.
