title: The beneficial effect of Radix Dipsaci total saponins on bone metabolism in vitro and in vivo and the possible mechanisms of action.
abstract: The purpose of this study is to investigate the anti-osteoporotic effects of Radix Dipsaci total saponins (RTS). We showed that RTS was able to improve bone properties by either an increase of osteoblastic activity or a decrease in osteoclastic activity.
  
  
  BACKGROUND
  Radix Dipsaci has long been used as an anti-osteoporotic drug. The present study investigates the anti-osteoporotic effects of RTS.
  
  
  METHODS
  Three-month-old female rats were randomly assigned into a sham-operated group (sham) and five ovariectomy (OVX) subgroups, namely, OVX with vehicle (OVX), OVX with 17β-ethinylestradiol (E(2)), and OVX with graded doses of RTS (50, 100, or 200 mg/kg/d). RTS and E(2) were administered orally, daily from 1 week after OVX treatment for 4 months. Bone mass, turnover, and strength were evaluated by dual-energy X-ray absorptiometry, biochemical markers, and the three-point bending test. The trabecular bone microarchitecture was assessed by microCT. In vitro experiments were performed to determine the potential molecular mechanisms of the anti-osteoporotic effect of RTS.
  
  
  RESULTS
  RTS prevented the loss of bone mass induced by OVX. The preventive effect on bone loss was primarily indicated by decreasing levels of bone turnover markers and confirmed by the changes in urinary calcium and phosphorus excretion. The treatment also enhanced the biomechanical strength of bone and prevented the deterioration of trabecular bone microarchitecture. RTS induced MC3T3-E1 and primary osteoblastic cell maturation and differentiation and increased bone formation by increasing BMP-2 synthesis. In addition, RTS inhibited osteoclastogenesis through an increase in osteoprotegrin and a decrease in NF-kB ligand expression in vitro.
  
  
  CONCLUSIONS
  RTS treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.
authors.affiliation: School of Life Sciences, Northwestern Polytechnical University, Xi'an, 710072, People's Republic of China.
authors.forename: Y B
authors.initials: YB
authors.lastname: Niu
authors.forename: Y H
authors.initials: YH
authors.lastname: Li
authors.forename: X H
authors.initials: XH
authors.lastname: Kong
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: Q B
authors.initials: QB
authors.lastname: Mei
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D049917:Dipsacaceae; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000096:biosynthesis; D010052:Ovariectomy; D010758:Phosphorus / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000473:pathology
chemical_list: C525720:Bmp2 protein, rat; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004365:Drugs, Chinese Herbal; D053244:Osteoprotegerin; D053245:RANK Ligand; D012503:Saponins; C506032:Tnfrsf11b protein, rat; D010758:Phosphorus; D004958:Estradiol; D002118:Calcium