title: Root bark of Sambucus Williamsii Hance promotes rat femoral fracture healing by the BMP-2/Runx2 signaling pathway.
abstract: BACKGROUND
  Sambucus Williamsii Hance (SWH) is a plant from a family of Caprifoliaceae, which has a long medical history of use as an effective folk treatment for fracture bruises.
  
  
  OBJECTIVE
  To evaluate the effects of 50% ethanol extracts of root-bark of Sambucus Williamsii Hance(EE-rbSWH) on fracture healing of rats and explore its mechanism of actions related to the BMP-2 signaling pathway.
  
  
  METHODS
  EE-rbSWH was orally administered at the doses of 340 and 680mg/kg to adult Sprague-Dawley rats with operation of open femur fracture completely for 2, 4 and 8 weeks. And the rats of sham operation and Model groups were administered Vehicle (distilled water 0.8mL/200g/day). Firstly, the bone X-ray morphology and bone mineral density(BMD) of the fracture site were observed and measured after anesthesia the rats at weeks 2, 4, and 8 after surgery, then the serum levels of alkaline phosphatase(ALP) and osteocalcin (BGP) were measured; Secondly, the tissue morphology of the fracture site was observed after sacrificed the rats; Thirdly, the formation of mineralized nodules in bone marrow stromal cells(BMSC) were evaluated at week 2; Lastly, the genes levels of BMP-2 and Runx2 in the femur were detected at week 2 and 4, and the proteins expression of BMP-2 signaling pathway (BMP-2, BMPRIB, BMPRII and Runx2) in the femur also were detected at week 2.
  
  
  RESULTS
  EE-rbSWH remarkably accelerated fracture healing by promoting bone formation at all the time points of fracture healing. Mainly by increasing the BMD level at the fracture site, the levels of serum ALP and BGP, and also the numbers increasing of calcified nodules in BMSC. The mechanism studies, EE-rbSWH can promote fracture healing by enhancing the expressions of BMP-2 and Runx2 mRNA, and also the proteins of BMP-2, BMPRIB, BMPRII and Runx2 at the fracture site of rats.
  
  
  CONCLUSIONS
  Our results suggested that 50% ethanol extracts of root-bark of Sambucus Williamsii Hance can accelerate fracture healing by recruitment of osteoblasts at the fracture site and through up-regulation of the BMP-2 signaling pathway.
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Bingyou
authors.initials: B
authors.lastname: Yang
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lin
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Tan
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xian
authors.initials: X
authors.lastname: She
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key laboratory of Chinese Materia Medica, Ministry of Education, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: hxkuang@hotmail.com.
authors.forename: Haixue
authors.initials: H
authors.lastname: Kuang
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000737:chemistry; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000097:blood; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D027923:Sambucus / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C525720:Bmp2 protein, rat; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D010936:Plant Extracts; C493717:Runx2 protein, rat; D012997:Solvents; D015675:Osteocalcin; D000431:Ethanol; C498216:Bmpr1b protein, rat; C498220:Bmpr2 protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D000469:Alkaline Phosphatase
keywords: BMP-2; BMPRs; Bone marrow stromal cells; Fracture healing; Root-bark of Sambucus Williamsii Hance; Runx2