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. Conclusion The BMP-2/Smad pathway is involved in
Sr-induced osteoblast differentiation of rat BMSCs.