Synergistic action of transforming growth factor-β and insulin-like growth factor-I induces expression of type II collagen and aggrecan genes in adult human articular chondrocytes

被引:229
作者
Yaeger, PC [1 ]
Masi, TL [1 ]
de Ortiz, JLB [1 ]
Binette, F [1 ]
Tubo, R [1 ]
McPherson, JM [1 ]
机构
[1] Genzyme Tissue Repair, Framingham, MA 01701 USA
关键词
D O I
10.1006/excr.1997.3781
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Reexpression of aggrecan and type II collagen genes in dedifferentiated adult human articular chondro cytes (AHAC) in suspension culture varied widely depending on the specific lot of bovine serum used to supplement the culture medium. Some lots of serum provided strong induction of aggrecan and type II collagen expression by AHAC while others did not stimulate significant production of these hyaline cartilage extracellular matrix molecules even following several weeks in culture. Addition of 50 ng/ml insulin-like growth factor-I (IGF-I) to a deficient serum lot significantly enhanced its ability to induce aggrecan and type II collagen mRNA. Given this observation, IGF-I and other growth factors were tested in defined serum-free media for their effects on the expression of these genes. Neither IGF-I nor insulin nor transforming growth factor beta (TGF-beta) alone stimulated induction of aggrecan or type II collagen production by dedifferentiated AHAC. However, TGF-beta 1 or TGF-beta 2 combined with IGE-I or insulin provided a strong induction as demonstrated by RNase protection and immunohistochemical assays. Interestingly, type I collagen, previously shown to be downregulated in serum supplemented suspension cultures of articular chondrocytes, persisted for up to 12 weeks in AHAC cultured in defined medium supplemented with TGF-beta and IGF-I. (C) 1997 Academic Press.
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收藏
页码:318 / 325
页数:8
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