title: [Strontium ranelate promotes osteogenic differentiation of rat bone mesenchymal stem cells through bone morphogenetic protein-2/Smad signaling pathway].
abstract: OBJECTIVE
  To explore whether strontium ranelate (Sr) promotes osteoblast lineage differentiation of rat bone mesenchymal stem cells (BMSCs) through the bone morphogenetic protein-2 (BMP-2)/Smad signaling pathway.
  
  
  METHODS
  Cultured rat BMSCs were exposed to different concentrations of Sr, noggin (an inhibitor of BMP-2) or Smad1 siRNA. The activity of alkaline phosphatase (ALP) in the exposed cells was detected by colorimetry, and the formation of mineralized nodules was observed with alizarin red staining. The expressions of phosphorylated (p) Smad1/5/8 and Runt-related transcription factor 2 (Runx2) in the cells were detected by Western blotting.
  
  
  RESULTS
  Exposure to Sr at 0.1 to 10 mmol/L for 1 h markedly increased the expression of p-Smad1/5/8 in the BMSCs, and the increment was the most obvious following 1 mmol/L Sr exposure. Preconditioning with 100 ng/ml noggin for 2 h inhibited Sr-induced up-regulation of p-Smad1/5/8 expressions. Exposure of the cells to 0.1 to 5 mmol/L Sr for 6 h significantly enhanced Runx2 expression, and the peak enhancement occurred following 1 mmol/L Sr exposure. Transfection of the BMSCs with Smad1 siRNA decreased the basal level of Smad1/5/8 protein expression, and also inhibited Sr-induced up-regulation of p-Smad1/5/8 and Runx2 expressions as well as Sr-induced enhancement of ALP activity and formation of mineralized nodules.
  
  
  CONCLUSIONS
  The BMP-2/Smad pathway is involved in Sr-induced osteoblast differentiation of rat BMSCs.
authors.affiliation: Southern Medical University, Guangzhou 510515, China. 541031834@qq.com
authors.forename: Huizhen
authors.initials: H
authors.lastname: Lv
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Huang
authors.forename: Sisi
authors.initials: S
authors.lastname: Jin
authors.forename: Runmin
authors.initials: R
authors.lastname: Guo
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D013324:Strontium / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D013876:Thiophenes; C081587:strontium ranelate; D000469:Alkaline Phosphatase; D013324:Strontium