FGF-2 increases osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells by inactivation of TGF-β signaling

被引:101
作者
Ito, Tomomi [1 ,2 ]
Sawada, Rumi [1 ]
Fujiwara, Yoko [1 ,2 ]
Tsuchiya, Toshie
机构
[1] Natl Inst Hlth, Div Med Devices, Setagaya Ku, Tokyo 1588501, Japan
[2] Ochanomizu Univ, Grad Sch Human & Sci, Tokyo 1128610, Japan
关键词
mesenchymal stem cells; fibroblast growth factor-2; insulin-like growth factor-I; transforming growth factor-beta; osteogenic differentiation; chondrogenic differentiation;
D O I
10.1007/s10616-007-9092-1
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Human mesenchymal stem cells (hMSCs) are able to self-replicate and differentiate into a variety of cell types including osteoblasts, chondrocytes, adipocytes, endothelial cells, and muscle cells. It was reported that fibroblast growth factor-2 (FGF-2) increased the growth rate and multidifferentiation potentials of hMSCs. In this study, we investigated the genes involved in the promotion of osteogenic and chondrogenic differentiation potentials of hMSCs in the presence of FGF-2. hMSCs were maintained in the medium with FGF-2. hMSCs were harvested for the study of osteogenic or chondrogenic differentiation potential after 15 days' culture. To investigate osteogenic differentiation, the protein levels of alkaline phosphatase (ALP) and the mRNA expression levels of osteocalcin were measured after the induction of osteogenic differentiation. Moreover, the investigation for chondrogenic differentiation was performed by measuring the mRNA expression levels of type II and type X collagens after the induction of chondrogenic differentiation. The expression levels of ALP, type II collagen, and type X collagen of hMSCs cultured with FGF-2 were significantly higher than control. These results suggested that FGF-2 increased osteogenic and chondrogenic differentiation potentials of hMSCs. Furthermore, microarray analysis was performed after 15 days' culture in the medium with FGF-2. We found that the overall insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) signaling pathways were inactivated by FGF-2. These results suggested that the inactivation of IGF-I and TGF-beta signaling promotes osteogenic and chondrogenic differentiation potential of hMSCs in the presence of FGF-2.
引用
收藏
页码:1 / 7
页数:7
相关论文
共 13 条
[1]   Mesenchymal stem cells: building blocks for molecular medicine in the 21st century [J].
Caplan, AI ;
Bruder, SP .
TRENDS IN MOLECULAR MEDICINE, 2001, 7 (06) :259-264
[2]   FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-β2 [J].
Ito, Tomomi ;
Sawada, Rumi ;
Fujiwara, Yoko ;
Seyama, Yousuke ;
Tsuchiya, Toshie .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 359 (01) :108-114
[3]   Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells [J].
Kakudo, Natsuko ;
Shimotsuma, Ayuko ;
Kusumoto, Kenji .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 359 (02) :239-244
[4]   Osteoblast recruitment from stem cells does not decrease by age at late adulthood [J].
Leskelä, HV ;
Risteli, J ;
Niskanen, S ;
Koivunen, J ;
Ivaska, KK ;
Lehenkari, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 311 (04) :1008-1013
[5]   Articular cartilage repair using tissue engineering technique-novel approach with minimally invasive procedure [J].
Ochi, M ;
Adachi, N ;
Nobuto, H ;
Yanada, S ;
Ito, Y ;
Agung, M .
ARTIFICIAL ORGANS, 2004, 28 (01) :28-32
[6]   Tissue-engineered bone regeneration [J].
Petite, H ;
Viateau, V ;
Bensaïd, W ;
Meunier, A ;
de Pollak, C ;
Bourguignon, M ;
Oudina, K ;
Sedel, L ;
Guillemin, G .
NATURE BIOTECHNOLOGY, 2000, 18 (09) :959-963
[7]   Multilineage potential of adult human mesenchymal stem cells [J].
Pittenger, MF ;
Mackay, AM ;
Beck, SC ;
Jaiswal, RK ;
Douglas, R ;
Mosca, JD ;
Moorman, MA ;
Simonetti, DW ;
Craig, S ;
Marshak, DR .
SCIENCE, 1999, 284 (5411) :143-147
[8]   FGF-2 inhibits osteogenesis in mouse adipose tissue-derived stromal cells and sustains their proliferative and osteogenic potential state [J].
Quarto, Natalina ;
Longaker, Michael T. .
TISSUE ENGINEERING, 2006, 12 (06) :1405-1418
[9]   Changes in expression of genes related to cell proliferation in human mesenchymal stem cells during in vitro culture in comparison with cancer cells [J].
Sawada R. ;
Ito T. ;
Tsuchiya T. .
Journal of Artificial Organs, 2006, 9 (3) :179-184
[10]   FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells [J].
Solchaga, LA ;
Penick, K ;
Porter, JD ;
Goldberg, VM ;
Caplan, AI ;
Welter, JF .
JOURNAL OF CELLULAR PHYSIOLOGY, 2005, 203 (02) :398-409