title: Lithium prevents rat steroid-related osteonecrosis of the femoral head by β-catenin activation.
abstract: 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-Tyr(216) 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-Tyr(216) 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.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China. drfan2140@mail.xjtu.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005270:Femur Head / Q000187:drug effects* / Q000473:pathology; D005271:Femur Head Necrosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005938:Glucocorticoids / Q000009:adverse effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D008055:Lipids; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride; D008775:Methylprednisolone
keywords: Angiogenesis; Lithium; Osteogenic/adipogenic differentiation disturbance; Steroid-related osteonecrosis; β-Catenin pathway