title: Ginsenoside Rg1 promotes osteogenic differentiation of rBMSCs and healing of rat tibial fractures through regulation of GR-dependent BMP-2/SMAD signaling.
abstract: Fracture healing is closely related to the number and activity of bone marrow mesenchymal stem cells (BMSCs) near the fracture site. The present study was to investigate the effect of Rg1 on osteogenic differentiation of cultured BMSCs and related mechanisms and on the fracture healing in a fracture model. In vitro experiments showed that Rg1 promoted the proliferation and osteogenic differentiation of BMSCs. Western blot analyses demonstrated that Rg1 promoted osteogenic differentiation of BMSCs through the glucocorticoid receptor (GR)-dependent BMP-2/Smad signaling pathway. In vivo, X-ray examination showed that callus growth in rats treated with Rg1 was substantially faster than that in control rats after fracture. The results of H&E and Safranin-O/Fast Green staining revealed that, compared with controls, rats in the Rg1 treatment group had a significantly higher proportion of trabecular bone but a much lower proportion of fibers and cartilage components inside the callus. Micro-CT suggested that bone mineral density (BMD), percent bone volume (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly increased in the treatment group, whereas trabecular separation (Tb.Sp) was significantly reduced. Thus, Rg1 promotes osteogenic differentiation by activating the GR/BMP-2 signaling pathway, enhances bone calcification, and ultimately accelerates the fracture healing in rats.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210000, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210000, China.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210000, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210000, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing 210000, China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Yin
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D017102:Fracture Healing; D036145:Ginsenosides / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis; D011859:Radiography; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013978:Tibial Fractures / Q000188:drug therapy*
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D002491:Central Nervous System Agents; D036145:Ginsenosides; D051785:Smad Proteins; C035054:ginsenoside Rg1