title: The beneficial effect of Icariin on bone is diminished in osteoprotegerin-deficient mice.
abstract: BACKGROUND
  Osteoprogeterin (OPG) plays an important role in regulating bone homeostasis by inhibiting osteoclastogenesis and bone resorption. Icariin is the major ingredient of Herba Epimedii, which exerts anabolic and anti-resorptive effects on bone, but the mechanism remains unknown. In this study, we evaluated the role of OPG in Icariin-mediated beneficial effects on bone.
  
  
  METHODS
  Twelve-week-old Opg knockout (KO) male mice and their wild type (WT) littermates were orally administered with Icariin (0.3 mg/g) everyday for 8 weeks. Bone mass and microstructure in the right proximal tibiae were analyzed with micro-computed tomography (μCT). Bone remodeling was evaluated with serum biochemical analyses and bone histomorphometry. The colonies of fibroblast and osteoblast from bone marrow derived cells were quantified. The mRNA expressions of osteoblast and osteoclast related genes in trabecular bone from the femora were analyzed by real-time PCR.
  
  
  RESULTS
  Icariin treatment led to greater trabecular bone volume and trabecular number compared with vehicle treatment in WT mice. Icariin treatment increased bone formation parameters while it decreased bone resorption parameters in WT mice; however, the anabolic response of trabecular bone to Icariin treatment was diminished in KO mice. At cellular and molecular levels, Icariin significantly increased the formation of osteoblast colonies from bone marrow derived cells and the Opg gene expression in trabecular bone of WT mice.
  
  
  CONCLUSIONS
  These data suggest that Icariin treatment exerted anabolic and anti-resorptive effects on trabecular bone of WT mice, in which the effects were diminished in KO mice. The effects of Icariin treatment on bone are dependent on up-regulation of Opg, therefore, OPG plays an essential role in Icariin-mediated beneficial effects on trabecular bone.
authors.affiliation: Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.forename: Songlin
authors.initials: S
authors.lastname: Peng
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Zeng-Wu
authors.initials: ZW
authors.lastname: Shao
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Wan-Xin
authors.initials: WX
authors.lastname: Zhen
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D005419:Flavonoids / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D053244:Osteoprotegerin / Q000172:deficiency* / Q000235:genetics
chemical_list: D005419:Flavonoids; D053244:Osteoprotegerin; C056599:icariin