南方医科大学学报2013,Vol.33Issue(3):376-381,6.DOI:10.3969/j.issn.1673-4254.2013.03.14
雷奈酸锶通过骨形态发生蛋白-2/Smad通路促进骨髓间充质干细胞成骨分化
Strontium ranelate promotes osteogenic differentiation of rat bone mesenchymal stem cells through bone morphogenetic protein-2/Smad signaling pathway
摘要
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 Smadl 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 Smadl 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.关键词
雷奈酸锶/骨髓间充质于细胞/骨形态发生蛋白-2/小RNA干扰/Smad1/5/8/Runx2/成骨细胞Key words
strontium ranelate/ bone mesenchymal stem cells/ bone morphogenetic protein-2/ small interfering RNA/ Smad1/5/ 8/ Runx2/ osteoblasts引用本文复制引用
吕辉珍,黄晓丹,靳思思,郭润民,吴文..雷奈酸锶通过骨形态发生蛋白-2/Smad通路促进骨髓间充质干细胞成骨分化[J].南方医科大学学报,2013,33(3):376-381,6.基金项目
广东省科技计划项目(2011B031800002) (2011B031800002)
广州市科技计划项目(2012J4300082) (2012J4300082)
广东省自然科学基金(S2012010009403) (S2012010009403)