RGD Reference Report - Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPAR¿ expression and activating Wnt signaling pathway. - Rat Genome Database

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Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPAR¿ expression and activating Wnt signaling pathway.

Authors: Jiang, Yini  Zhang, Yanqiong  Zhang, Haojun  Zhu, Bin  Li, Ping  Lu, Chao  Xu, Ying  Chen, Weiheng  Lin, Na 
Citation: Jiang Y, etal., Exp Biol Med (Maywood). 2014 Mar;239(3):347-55. doi: 10.1177/1535370213519215. Epub 2014 Feb 7.
RGD ID: 12793062
Pubmed: PMID:24510055   (View Abstract at PubMed)
DOI: DOI:10.1177/1535370213519215   (Journal Full-text)

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is characterized by increase of intraosseous pressure because of lipid metabolism disturbance such as elevation of adipogenesis and fat cell hypertrophy in the bone marrow, subsequently leading to disturbances of coagulation-fibrinolysis system in the femoral head and finally resulting in bone ischemia. Pravastatin has been demonstrated to be useful in preventing steroid-induced ONFH in animal models. However, its exact mechanisms acting on this disease have not been fully elucidated. To address this problem, steroid-induced ONFH rat model was constructed to evaluate the effects of pravastatin treatment on the osteonecrotic changes and repair processes. Then, Micro-CT-based micro-angiography was performed to assess the effects of pravastatin treatment on vascularization. In addition, serum lipid levels were detected by haematological examination. After that, the expression of peroxisome proliferator-activated receptor gamma (PPARγ), Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5), ß-catenin and runt-related transcription factor 2 (RUNX2) at both mRNA and protein levels were further detected by immunohistochemistry, real-time quantitative PCR, and Western blot analyses. The results, the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were dramatically lower in the pravastatin treatment groups than in the model group (all P¿<¿0.05). Moreover, by micro-CT quantification, pravastatin treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads of steroid-induced ONFH rats. Importantly, pravastatin treatment could prevent steroid-induced ONFH by suppressing the expression of PPARγ, and increasing the expression of Wnt3a, LRP5, ß-catenin, and RUNX2, at both mRNA and protein levels, in the femoral heads of steroid-induced ONFH rats. In conclusion, Pravastatin may prevent steroid-induced ONFH by suppressing PPARγ expression and activating Wnt signaling pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Femur Head Necrosis treatmentISOLrp5 (Rattus norvegicus)12793062; 12793062 RGD 
Femur Head Necrosis treatmentIEP 12793062 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lrp5  (LDL receptor related protein 5)

Genes (Mus musculus)
Lrp5  (low density lipoprotein receptor-related protein 5)

Genes (Homo sapiens)
LRP5  (LDL receptor related protein 5)


Additional Information