Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2

被引:29
作者
Song, Tao [1 ]
Wang, Wenjuan [1 ]
Xu, Jing [1 ]
Zhao, Dan [1 ]
Dong, Qian [1 ]
Li, Li [1 ]
Yang, Xue [1 ]
Duan, Xinglian [1 ]
Liang, Yiwen [1 ]
Xiao, Yan [1 ]
Wang, Jin [1 ]
He, Juanwen [1 ]
Tang, Ming [1 ]
Wang, Jian [1 ]
Luo, Jinyong [1 ]
机构
[1] Chongqing Med Univ, Chinese Minist Educ, Key Lab Diagnost Med, Chongqing 40016, Peoples R China
基金
中国国家自然科学基金;
关键词
Fibroblast growth factor 2; Bone morphogenic proteins 9; Osteogenic differentiation; Mesenchymal stem cells; Smads; EXPRESSION; RECEPTORS; REPAIR; GENE; OSTEOCALCIN; ACTIVATION; INDUCTION; BMP-9; FGF2;
D O I
10.1016/j.biocel.2013.05.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of mesenchymal stem cells (MSCs) and BMPs in bone tissue engineering. BMP9 is highly capable of promoting osteogenic differentiation of MSCs. Fibroblast growth factor 2 (FGF2) is abundantly secreted during the healing process of fractures or in surgery bone sites. Herein, we explore the detail effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. It was found that FGF2 inhibited BMP9-induced osteogenic differentiation by blocking BMP9-induced Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2 in MSCs. This effect was rescued by exogenous expression of ALK1 and ALK2, which are proved to be receptors for BMP9. Our results discovered a clue to explain the mechanism involved in the inhibitory effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. This crosstalk between FGF2 and BMP9 should be emphasized in the future use of BMP9 in therapeutic purpose of fracture repair. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1639 / 1646
页数:8
相关论文
共 44 条
[1]   The Therapeutic Applications of Multipotential Mesenchymal/Stromal Stem Cells in Skeletal Tissue Repair [J].
Arthur, Agnieszka ;
Zannettino, Andrew ;
Gronthos, Stan .
JOURNAL OF CELLULAR PHYSIOLOGY, 2009, 218 (02) :237-245
[2]   Induction of Olig2+ Precursors by FGF Involves BMP Signalling Blockade at the Smad Level [J].
Bilican, Bilada ;
Fiore-Heriche, Christelle ;
Compston, Alastair ;
Allen, Nicholas D. ;
Chandran, Siddharthan .
PLOS ONE, 2008, 3 (08)
[3]   Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells [J].
Biver, Emmanuel ;
Soubrier, Anne-Sophie ;
Thouverey, Cyril ;
Cortet, Bernard ;
Broux, Odile ;
Caverzasio, Joseph ;
Hardouin, Pierre .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 427 (04) :737-742
[4]  
BOLANDER ME, 1992, P SOC EXP BIOL MED, V200, P165
[5]   Complications of Recombinant Human BMP-2 for Treating Complex Tibial Plateau Fractures: A Preliminary Report [J].
Boraiah, Sreevathsa ;
Paul, Omesh ;
Hawkes, David ;
Wickham, Matthew ;
Lorich, Dean G. .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2009, 467 (12) :3257-3262
[6]   The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects [J].
Bruder, SP ;
Kraus, KH ;
Goldberg, VM ;
Kadiyala, S .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1998, 80A (07) :985-996
[7]   EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR ON BONE-FORMATION INVITRO [J].
CANALIS, E ;
CENTRELLA, M ;
MCCARTHY, T .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (05) :1572-1577
[8]   An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis [J].
Chen, C ;
Grzegorzewski, KJ ;
Barash, S ;
Zhao, QH ;
Schneider, H ;
Singh, M ;
Pukac, L ;
Bell, AC ;
Duan, R ;
Coleman, T ;
Duttaroy, A ;
Cheng, S ;
Hirsch, J ;
Zhang, LY ;
Lazard, Y ;
Fischer, C ;
Barber, MC ;
Ma, ZD ;
Zhang, YQ ;
Reavey, P ;
Zhong, LL ;
Teng, BQ ;
Sanyal, I ;
Ruben, SM ;
Blondel, O ;
Birse, CE .
NATURE BIOTECHNOLOGY, 2003, 21 (03) :294-301
[9]   Bone morphogenetic proteins [J].
Chen, D ;
Zhao, M ;
Mundy, GR .
GROWTH FACTORS, 2004, 22 (04) :233-241
[10]   Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells [J].
Cushing, Melinda C. ;
Mariner, Peter D. ;
Liao, Jo-Tsu ;
Sims, Evan A. ;
Anseth, Kristi S. .
FASEB JOURNAL, 2008, 22 (06) :1769-1777