title: Ginsenosides Rg3 attenuates glucocorticoid-induced osteoporosis through regulating BMP-2/BMPR1A/Runx2 signaling pathway.
abstract: Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX)-induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone-alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy.
authors.affiliation: Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, People's Republic of China.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Third Department of Orthopaedic Surgery, The People's Hospital of China Medical University, Shenyang 110016, People's Republic of China. Electronic address: Baixizh_65@163.com.
authors.forename: Xizhuang
authors.initials: X
authors.lastname: Bai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003907:Dexamethasone / Q000009:adverse effects*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D036145:Ginsenosides / Q000627:therapeutic use*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D036145:Ginsenosides; C097367:ginsenoside Rg3; D003907:Dexamethasone; C498213:Bmpr1a protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: BMP-2; Ginsenosides Rg3; Glucocorticoid; Osteoblast; Osteoporosis