SYNERGISTIC ACTION OF TRANSFORMING-GROWTH-FACTOR-BETA AND INSULIN-LIKE GROWTH-FACTOR-I INDUCES EXPRESSION OF TYPE-II COLLAGEN AND AGGRECAN GENES IN ADULT HUMAN ARTICULAR CHONDROCYTES
Pc. Yaeger et al., SYNERGISTIC ACTION OF TRANSFORMING-GROWTH-FACTOR-BETA AND INSULIN-LIKE GROWTH-FACTOR-I INDUCES EXPRESSION OF TYPE-II COLLAGEN AND AGGRECAN GENES IN ADULT HUMAN ARTICULAR CHONDROCYTES, Experimental cell research, 237(2), 1997, pp. 318-325
Reexpression of aggrecan and type II collagen genes in dedifferentiate
d adult human articular chondro cytes (AHAC) in suspension culture var
ied widely depending on the specific lot of bovine serum used to suppl
ement 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 extrac
ellular matrix molecules even following several weeks in culture. Addi
tion of 50 ng/ml insulin-like growth factor-I (IGF-I) to a deficient s
erum lot significantly enhanced its ability to induce aggrecan and typ
e II collagen mRNA. Given this observation, IGF-I and other growth fac
tors 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 o
r type II collagen production by dedifferentiated AHAC. However, TGF-b
eta 1 or TGF-beta 2 combined with IGE-I or insulin provided a strong i
nduction as demonstrated by RNase protection and immunohistochemical a
ssays. Interestingly, type I collagen, previously shown to be downregu
lated in serum supplemented suspension cultures of articular chondrocy
tes, persisted for up to 12 weeks in AHAC cultured in defined medium s
upplemented with TGF-beta and IGF-I. (C) 1997 Academic Press.