Lithium prevents rat steroid-related osteonecrosis of the femoral head by β-catenin activation
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This study explored the use of lithium to prevent rat steroid-related osteonecrosis of the femoral head (ONFH) through the modulation of the β-catenin pathway. ONFH was induced by methylprednisolone combined with lipopolysaccharide, and serum lipids were analyzed. ONFH was detected by hematoxylin–eosin staining. Micro-CT-based angiography and bone scanning were performed to analyze vessels and bone structure, respectively. Immunohistochemical staining for peroxisome proliferator-activated receptor gamma (PPARγ), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was analyzed. Protein levels of phospho-glycogen synthase kinase-3β at Tyr-216 (p-Tyr216 GSK-3β), total glycogen synthase kinase-3β (GSK-3β) and β-catenin, as well as mRNA levels of GSK-3β and β-catenin in femoral heads, were assessed. The rate of empty bone lacunae in the femoral heads was lower in the lithium and control groups than in the model group. The lithium group showed preventive effects against steroid-related vessel loss by micro-CT-based angiography and VEGF staining. Lithium treatment improved hyperlipidemia and reduced PPARγ expression. Moreover, lithium improved steroid-related bone loss in micro-CT bone scans and BMP-2 staining analyses. Furthermore, local β-catenin was reduced in steroid-related ONFH, and lithium treatment increased β-catenin expression while reducing p-Tyr216 GSK-3β levels. The local β-catenin pathway was inhibited during steroid-related ONFH. Lithium may enhance angiogenesis and stabilize osteogenic/adipogenic homeostasis during steroid-related ONFH in rats by activating the β-catenin pathway.
KeywordsLithium Steroid-related osteonecrosis β-Catenin pathway Angiogenesis Osteogenic/adipogenic differentiation disturbance
This work was supported by the National Natural Science Foundation of China (Nos. 81101363, 81371944 and 81572145) and the Fundamental Research Funds for the Central Universities.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
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