title: Neurotrophine-3 may contribute to neuronal differentiation of mesenchymal stem cells through the activation of the bone morphogenetic protein pathway.
abstract: We investigated whether neurotrophin-3 (NT-3) can promote differentiation of mouse bone mesenchymal stem cells (MSCs) into neurons via the bone morphogenetic protein pathway. MSCs were prepared from rat bone marrow and either transfected with pIRES2-EGFP or pIRES2-EGFP-NT-3 or treated with bone morphogenetic protein 4. The pIRES2-EGFP-NT-3-transfected MSCs further underwent noggin treatment or siRNA-mediated knockout of the TrkC gene or were left untreated. Immunofluorescence staining, real-time PCR and Western blot analyses were performed to evaluate the transcription and expression of neural-specific genes and BMP-Smad signaling. MSCs were efficiently transduced by the NT-3 gene via pIRES2-EGFP vectors. pIRES2- EGFP-NT-3 could initiate the transcription and expression of neural-specific genes, including nestin, NSE and MAP-2, and stimulate BMP-Smad signaling. The transcription and expression of neural-specific genes and BMP-Smad signaling were significantly suppressed by siRNA-mediated knockdown of the TrkC gene of MSCs. These findings suggest that the BMP signaling pathway may be a key regulatory point in NT-3-transfected neuronal differentiation of MSCs. The BMP and neurotrophin pathways contribute to a tightly regulated signaling network that directs the precise connections between neuronal differentiation of MSCs and their targets.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Li
authors.forename: Hongkun
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D005904:Glial Fibrillary Acidic Protein; C577486:Nes protein, rat; D064231:Nestin; D020933:Neurotrophin 3; D051898:Smad1 Protein; D049452:Green Fluorescent Proteins