title: [Insulin-like growth factor 1 induces bone mesenchymal stem cells differentiation into cardiomyocyte-like cells].
abstract: OBJECTIVE
  To explore the ability and mechanism of insulin-like growth factor 1 (IGF-1) induced bone mesenchymal stem cells (BMSCs) differentiation into cardiomyocyte-like cells (CLCs).
  
  
  METHODS
  BMSCs were isolated and purified in vitro. BMSCs were treated with control medium and 15 ng/ml IGF-1 for 3, 7, 14 and 21 d, respectively. The expression of Troponin-T (TNT), Troponin-I (TNI) and pIGF-1R were detected by immunocytochemistry and Western blot. In another experimental setting, BMSCs were treated with control medium and 15 ng/ml IGF-1, IGF-1 antagonist I-OMe AG538 (300 nmol/L) and 300 nmol/L I-OMe AG538 + 15 ng/ml IGF-1 for 3 to 48 h, respectively. Phosphorylation status of ERK1/2 and AKT, the two downstream mediators of mitogen-activated protein kinase (MAPK) kinase and phosphatidylinositol 3-kinase (PI3K) pathways, were detected by immunocytochemistry and Western blot.
  
  
  RESULTS
  After 3 to 21 d exposure to IGF-1, the expression of pIGF-1R, TNT and TNI were significantly higher in IGF-1 group than those in control group, pIGF-1R peaked 14 d (all P < 0.05). After 3 and 6 h treatment, the ratio of pAKT/AKT (0.17 ± 0.03) and pERK1/2/ERK1/2 (0.06 ± 0.03) were significantly downregulated in I-OMe AG538 group compared to control group (1.00 ± 0.05) (all P < 0.05). The ratio of pAKT/AKT (1.00 ± 0.07) and pERK1/2/ERK1/2 (1.00 ± 0.09) were significantly upregulated in IGF-1 group compared to control group (0.72 ± 0.05) (all P < 0.05), but the ratio of pAKT/AKT (0.31 ± 0.10) and pERK1/2/ERK1/2 (0.39 ± 0.04) were significantly downregulated in I-OMe AG538 group compared to control group (0.63 ± 0.05) (all P < 0.05), the value of gray scale of TNT (195.06 ± 5.98) and TNI (198.32 ± 3.46) in I-OMe AG538 + IGF-1 group were significantly upregulated than that in IGF-1 group for TNT (188.70 ± 5.35) and TNI (176.10 ± 4.96) (all P < 0.05).
  
  
  CONCLUSIONS
  IGF-1 could induce BMSCs differentiation into CLCs in vitro by activating MAPK and PI3K signaling pathways.
authors.affiliation: Department of Xuzhou Cardiovascular Disease Institute, Xuzhou Central Hospital, Xuzhou 221009, China.
authors.forename: Xiu-li
authors.initials: XL
authors.lastname: Wang
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Lü
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Hai-bin
authors.initials: HB
authors.lastname: Gong
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D007334:Insulin-Like Growth Factor I