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J. Cell Biol.,
Volume 140, Number 2, January 26, 1998 409-418






* Department of Biochemistry, To examine the role of bone morphogenetic
protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN)
forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and
upper portions of chick embryo sternum, respectively.
We found that control sternal chondrocyte populations
expressed type IA, IB, and II BMP receptors as well as
BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal
(LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR-
II-expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and
upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper
sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II-expressing US cells exhibited
little alkaline phosphatase activity and type X collagen
gene expression, while the control US cells produced
both alkaline phosphatase and type X collagen. Both
DN-BMPR-II-expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we
examined the effects of DN forms of types IA and IB
BMP receptors, we found that DN-BMPR-IA had little
effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by
the type II BMP receptor, is required for maintenance
of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.
Department of Oral Anatomy and Developmental Biology, Osaka University Faculty of
Dentistry, Osaka 565, Japan; § Department of Molecular Biology, Kawasaki Medical School, Kurashiki 701-71, Japan; and
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Tokushima City 770, Japan
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