Transforming growth factor-β1 induced alteration of skeletal morphogenesis in vivo

被引:27
作者
Ferguson, CM [1 ]
Schwarz, EM [1 ]
Puzas, JE [1 ]
Zuscik, MJ [1 ]
Drissi, H [1 ]
O'Keefe, RJ [1 ]
机构
[1] Univ Rochester, Sch Med & Dent, Ctr Musculoskeletal Res, Dept Orthopaed, Rochester, NY 14642 USA
关键词
transforming growth factor-beta; chondrocyte biology; chondrocyte maturation; embryonic limb development; chondrocyte proliferation;
D O I
10.1016/j.orthres.2003.10.023
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
Transforming growth factor beta (TGF-beta) is expressed in the growth plate and is an important regulator of chondrocyte maturation. Loss of function results in premature chondrocyte maturation both in vitro and in vivo. While TGF-beta inhibits chondrocyte maturation in cell cultures, the effect of increased TGF-beta has not been well characterized in an ill vivo development model. Addition of Affi-gel agarose beads loaded with TGF-beta1 (10 ng/mul) to developing stage 24-25 chick limb buds resulted in limb shortening and altered morphology. In situ hybridization studies showed down regulation of Indian hedgehog (ihh), bone morphogenetic protein 6 (bmp6), and collagen type X (colX) expression, markers of chondrocyte maturation, in TGF-beta1 treated limbs. TGF-beta1 also decreased chondrocyte proliferation in the developing anlage. The findings confirm a critical role for TGF-beta during skeletal development. A more complete understanding of the role of TGF-beta and its down-stream signals will lead to improved understanding and treatment of cartilage diseases. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:687 / 696
页数:10
相关论文
共 41 条
[1]   The perichondrium plays an important role in mediating the effects of TGF-β1 on endochondral bone formation [J].
Alvarez, J ;
Horton, J ;
Sohn, P ;
Serra, R .
DEVELOPMENTAL DYNAMICS, 2001, 221 (03) :311-321
[2]   TGF-BETA-1 PREVENTS HYPERTROPHY OF EPIPHYSEAL CHONDROCYTES - REGULATION OF GENE-EXPRESSION FOR CARTILAGE MATRIX PROTEINS AND METALLOPROTEASES [J].
BALLOCK, RT ;
HEYDEMANN, A ;
WAKEFIELD, LM ;
FLANDERS, KC ;
ROBERTS, AB ;
SPORN, MB .
DEVELOPMENTAL BIOLOGY, 1993, 158 (02) :414-429
[3]   SOX9 directly regulates the type-II collagen gene [J].
Bell, DM ;
Leung, KKH ;
Wheatley, SC ;
Ng, LJ ;
Zhou, S ;
Ling, KW ;
Sham, MH ;
Koopman, P ;
Tam, PPL ;
Cheah, KSE .
NATURE GENETICS, 1997, 16 (02) :174-178
[4]   Antagonistic effects of FGF4 on BMP induction of apoptosis and chondrogenesis in the chick limb bud [J].
Buckland, RA ;
Collinson, JM ;
Graham, E ;
Davidson, DR ;
Hill, RE .
MECHANISMS OF DEVELOPMENT, 1998, 71 (1-2) :143-150
[5]  
D'Angelo M, 2000, J CELL BIOCHEM, V77, P678, DOI 10.1002/(SICI)1097-4644(20000615)77:4<678::AID-JCB15>3.0.CO
[6]  
2-P
[7]   Authentic matrix vesicles contain active metalloproteases (MMP) -: A role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-β [J].
D'Angelo, M ;
Billings, PC ;
Pacifici, M ;
Leboy, PS ;
Kirsch, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (14) :11347-11353
[8]  
DERYNCK R, 1997, BIOCHIM BIOPHYS ACTA, V1333, pF85
[9]  
Ferguson CM, 2000, ENDOCRINOLOGY, V141, P4728, DOI 10.1210/en.141.12.4728
[10]  
Ganan Y, 1996, DEVELOPMENT, V122, P2349