Noggin and bone morphogenetic protein-4 coordinately regulate the progression of chondrogenic differentiation in mouse clonal EC cells, ATDC5.

Here we report the gene expression and regulation and the function of noggin in clonal mouse chondrogenic EC cells, ATDC5. In ATDC5 cells, the expression of Noggin mRNA increased in parallel with the progression of chondrogenic differentiation. The treatment with conditioned medium of noggin-transfected COS-7 cells decreased the levels of type II and type X collagen gene transcripts of differentiated ATDC5 cells in a dose-dependent manner, and this inhibitory action was reversed by exogenously administered BMP-4 in a dose-dependent manner. The steady-state level of noggin gene transcripts was markedly upregulated by exogenously administered BMP-4 in time- and dose-dependent manners. Furthermore, this stimulatory effect of BMP-4 was attenuated by treatment with actinomycin D, but not with cycloheximide. These results indicate that noggin and BMP-4 coordinately regulate the progression of chondrogenic differentiation in ATDC5 cells. Copyright 1999 Academic Press.