title: Kinsenoside prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis by regulating classical NF-κB pathways.
abstract: Kinsenoside is able to improve bone turnover rate in ovariectomized (OVX) mice. In vitro analysis shows that kinsenoside antagonizes osteoclast development and bone resorption.
  
  
  BACKGROUND
  Kinsenoside, the main active compound of the traditional Taiwanese herb Anoectochilus formosanus, has an antiinflammatory effect. This study investigates whether kinsenoside inhibits osteoporosis and osteoclastogenesis.
  
  
  METHODS
  OVX mice were used to examine the antiosteoporotic activity of kinsenoside. The trabecular bone microarchitecture was assessed by microcomputed tomography. In vitro experiments were performed to determine the mechanisms of the antiosteoporotic effects of kinsenoside.
  
  
  RESULTS
  Microcomputed tomography scanning showed that kinsenoside suppresses bone loss in OVX mice. Kinsenoside decreases plasma CTx concentration. Reverse transcription polymerase chain reaction (RT-PCR) analysis also showed that kinsenoside reduces the femoral mRNA expression of tartrate-resistant acid phosphatase (TRAP) and matrix metalloproteinase-9 (MMP-9). Kinsenoside inhibits osteoclast formation in bone marrow cells (BMs) and RAW 264.7 cells. Western blot was used to analyze osteoclast-associated signaling pathways in RAW 264.7 cells. Results show that kinsenoside does not inhibit IKK phosphorylation but suppresses the phosphorylation of IκBα and p65. Kinsenoside significantly inhibits the RANKL induction of IKK activity. Kinsenoside inhibits the RANKL-triggered nuclear translocations of NF-κB and nuclear factor of activated T cells c1 (NFATc1). RT-PCR was used to analyze osteoclast precursor fusion and resorption-associated gene expression in BMs. Kinsenoside inhibits the expression of cathepsin K (CAK), dendritic cell-specific transmembrane protein, MMP-9, and TRAP.
  
  
  CONCLUSIONS
  Kinsenoside inhibits osteoclastogenesis from macrophages by attenuating RANKL-induced NF-κB and NFATc1 activities, which in turn, prevents bone loss from OVX mice.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: H-B
authors.initials: HB
authors.lastname: Hsiao
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: J-B
authors.initials: JB
authors.lastname: Wu
authors.forename: W-C
authors.initials: WC
authors.lastname: Lin
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009005:Monosaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010024:Osteoporosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D055114:X-Ray Microtomography
chemical_list: C422363:3-glucopyranosyloxybutanolide; D050071:Bone Density Conservation Agents; D009005:Monosaccharides; D016328:NF-kappa B; D053245:RANK Ligand; D015107:4-Butyrolactone