title: TGF-β3 and IGF-1 synergy ameliorates nucleus pulposus mesenchymal stem cell differentiation towards the nucleus pulposus cell type through MAPK/ERK signaling.
abstract: This study aimed to investigate the synergy between transforming growth factor beta 3 (TGF-β3) and insulin-like growth factor 1 (IGF-1) on nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) and the underlying mechanism using a serum-free culture system. NP-MSC proliferation and viability were measured using a CCK-8 assay and annexin V-FITC/propidium iodide, respectively. NP-MSCs in micromasses were investigated for differentiation towards nucleus pulposus cells (NPCs). SOX-9, collagen-I, collagen-II, aggrecan and decorin expressions were detected by RT-PCR and immunoblotting. Matrix deposition was assessed by sulfated glycosaminoglycan (sGAG) analysis. Novel chondrogenic and nucleus pulposus (NP) genes were detected to distinguish differentiated cell types. MAPK/ERK and TGF/Smad signaling pathways were also examined. As a result, the synergy between TGF-β3 and IGF-1 enhanced NP-MSC viability, extracellular matrix (ECM) biosynthesis and differentiation towards NPCs, partly through the activation of the MAPK/ERK signaling pathway. Therefore, the synergy between TGF-β3 and IGF-1 ameliorates NP-MSC viability, differentiation and promotes intervertebral disc regeneration.
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Tao
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Chengzhen
authors.initials: C
authors.lastname: Liang
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Fangcai
authors.initials: F
authors.lastname: Li
authors.affiliation: a Department of Orthopedics , 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Chen
mesh_terms: D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D024043:Collagen Type II / Q000096:biosynthesis; D058575:Decorin / Q000096:biosynthesis; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology / Q000254:growth & development*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D055758:SOX9 Transcription Factor / Q000096:biosynthesis; D051785:Smad Proteins / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
chemical_list: D053674:Aggrecans; D024042:Collagen Type I; D024043:Collagen Type II; D058575:Decorin; D055758:SOX9 Transcription Factor; D051785:Smad Proteins; D053782:Transforming Growth Factor beta3; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Insulin-like growth factor 1 (IGF-1); MAPK/ERK signaling pathwaymesenchymal stem cell; intervertebral disc; nucleus pulposus; transforming growth factor beta (TGF-β)