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.
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26 January 1998
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January 26 1998
Bone Morphogenetic Protein Signaling Is Required for Maintenance of Differentiated Phenotype, Control of Proliferation, and Hypertrophy in Chondrocytes
Motomi Enomoto-Iwamoto,
Motomi Enomoto-Iwamoto
*Department of Biochemistry, ‡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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Masahiro Iwamoto,
Masahiro Iwamoto
*Department of Biochemistry, ‡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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Yoshiki Mukudai,
Yoshiki Mukudai
*Department of Biochemistry, ‡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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Yasuhiko Kawakami,
Yasuhiko Kawakami
*Department of Biochemistry, ‡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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Tsutomu Nohno,
Tsutomu Nohno
*Department of Biochemistry, ‡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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Yoshinobu Higuchi,
Yoshinobu Higuchi
*Department of Biochemistry, ‡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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Seiji Takemoto,
Seiji Takemoto
*Department of Biochemistry, ‡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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Hideyo Ohuchi,
Hideyo Ohuchi
*Department of Biochemistry, ‡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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Sumihare Noji,
Sumihare Noji
*Department of Biochemistry, ‡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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Kojiro Kurisu
Kojiro Kurisu
*Department of Biochemistry, ‡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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Motomi Enomoto-Iwamoto
*Department of Biochemistry, ‡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
Masahiro Iwamoto
*Department of Biochemistry, ‡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
Yoshiki Mukudai
*Department of Biochemistry, ‡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
Yasuhiko Kawakami
*Department of Biochemistry, ‡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
Tsutomu Nohno
*Department of Biochemistry, ‡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
Yoshinobu Higuchi
*Department of Biochemistry, ‡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
Seiji Takemoto
*Department of Biochemistry, ‡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
Hideyo Ohuchi
*Department of Biochemistry, ‡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
Sumihare Noji
*Department of Biochemistry, ‡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
Kojiro Kurisu
*Department of Biochemistry, ‡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
Address all correspondence to Masahiro Iwamoto, Department of Oral Anatomy and Developmental Biology, Osaka University Faculty of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565, Japan. Tel.: 81-6-879-2872. Fax: 81-6-879-2875. E-mail: [email protected]
Received:
June 30 1997
Revision Received:
November 07 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1998
J Cell Biol (1998) 140 (2): 409–418.
Article history
Received:
June 30 1997
Revision Received:
November 07 1997
Citation
Motomi Enomoto-Iwamoto, Masahiro Iwamoto, Yoshiki Mukudai, Yasuhiko Kawakami, Tsutomu Nohno, Yoshinobu Higuchi, Seiji Takemoto, Hideyo Ohuchi, Sumihare Noji, Kojiro Kurisu; Bone Morphogenetic Protein Signaling Is Required for Maintenance of Differentiated Phenotype, Control of Proliferation, and Hypertrophy in Chondrocytes . J Cell Biol 26 January 1998; 140 (2): 409–418. doi: https://doi.org/10.1083/jcb.140.2.409
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