GDF-5/7 and bFGF Activate Integrin α2-Mediated Cellular Migration in Rabbit Ligament Fibroblasts

被引:38
作者
Date, Hirokazu [1 ]
Furumatsu, Takayuki [1 ]
Sakoma, Yoshimasa [1 ]
Yoshida, Aki [1 ]
Hayashi, Yuko [1 ]
Abe, Nobuhiro [1 ]
Ozaki, Toshifumi [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr, Kita Ku, Okayama 7008558, Japan
基金
日本学术振兴会;
关键词
ACL; MCL; bFGF; GDF-5/7; integrin alpha 2; ANTERIOR CRUCIATE LIGAMENT; ADHESION STRENGTH; GROWTH-FACTORS; CROSS-TALK; CELLS; MATRIX; EXPRESSION; PROLIFERATION; ACL;
D O I
10.1002/jor.20981
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Cellular activities responding to growth factors are important in ligament healing. The anterior cruciate ligament (ACL) has poor healing potential compared to the medial collateral ligament (MCL). To assess the differences, we investigated the proliferation, migration, adhesion, and matrix synthesis responding to growth factors in rabbit ACL and MCL fibroblasts. ACL cell proliferation to basic fibroblast growth factor (bFGF), bone morphogenetic protein-2, growth and differentiation factor (GDF)-5, and GDF-7 treatment was similar to that of MCL cells. GDF-5 enhanced Colla1 expression in ACL and MCL fibroblasts up to 4.7- and 17-fold levels of control, respectively. MCL fibroblasts showed stronger migration activities in response to bFGF and GDF-5 than ACL cells. GDF-5/7 and bFGF also changed the stress fiber formation and cellular adhesion by modulating the distribution of integrin alpha 2. Functional blocking analyses using anti-integrin alpha 2 antibodies revealed that cellular migration responding to growth factors depended on the integrin alpha 2-mediated adhesion on type I collagen. The expression of integrin alpha 2 was also increased by growth factors in both cells. Our results demonstrate that GDF-5/7 and bFGF stimulate cellular migration by modulating integrin alpha 2 expression and integrin alpha 2-dependent adhesion, especially in MCL fibroblasts. These findings suggest that the different healing potential between ACL and MCL may be caused by different cellular behavior in the integrin alpha 2-mediated cellular migration in response to growth factors. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:225-231, 20.10
引用
收藏
页码:225 / 231
页数:7
相关论文
共 29 条
[1]   Cross-talk between integrins α1β1 and α2β1 in renal epithelial cells [J].
Abair, Tristin D. ;
Sundaramoorthy, Munirathinam ;
Chen, Dong ;
Heino, Jyrki ;
Ivaska, Johanna ;
Hudson, Billy G. ;
Sanders, Charles R. ;
Pozzi, Ambra ;
Zent, Roy .
EXPERIMENTAL CELL RESEARCH, 2008, 314 (19) :3593-3604
[2]  
AbiEzzi S S, 1997, Iowa Orthop J, V17, P102
[3]  
Arnold J A, 1979, Am J Sports Med, V7, P305, DOI 10.1177/036354657900700601
[4]   Membrane type-1 matrix metalloproteinase (MT1-MMP) processing of pro-αv integrin regulates cross-talk between αvβ3 and α2β1 integrins in breast carcinoma cells [J].
Baciu, PC ;
Suleiman, EA ;
Deryugina, EI ;
Strongin, AY .
EXPERIMENTAL CELL RESEARCH, 2003, 291 (01) :167-175
[5]   In vitro comparison of human fibroblasts from intact and ruptured ACL for use in tissue engineering [J].
Brune, T. ;
Borel, A. ;
Gilbert, T. W. ;
Franceschi, J. P. ;
Badylak, S. F. ;
Sommer, P. .
EUROPEAN CELLS & MATERIALS, 2007, 14 :78-90
[6]  
Cabaud H E, 1979, Am J Sports Med, V7, P18, DOI 10.1177/036354657900700105
[7]  
FETTO JF, 1980, CLIN ORTHOP RELAT R, P29
[8]   MEDIAL COLLATERAL LIGAMENT HEALING - A MULTIDISCIPLINARY ASSESSMENT IN RABBITS [J].
FRANK, C ;
WOO, SLY ;
AMIEL, D ;
HARWOOD, F ;
GOMEZ, M ;
AKESON, W .
AMERICAN JOURNAL OF SPORTS MEDICINE, 1983, 11 (06) :379-389
[9]   Molecular biology and biomechanics of normal and healing ligaments - a review [J].
Frank, CB ;
Hart, DA ;
Shrive, NG .
OSTEOARTHRITIS AND CARTILAGE, 1999, 7 (01) :130-140
[10]   Endostatin inhibits adhesion of endothelial cells to collagen I via α2β1 integrin, a possible cause of prevention of chondrosarcoma growth [J].
Furumatsu, T ;
Yamaguchi, N ;
Nishida, K ;
Kawai, A ;
Kunisada, T ;
Namba, M ;
Inoue, H ;
Ninomiya, Y .
JOURNAL OF BIOCHEMISTRY, 2002, 131 (04) :619-626