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PMID:9442116

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Citation

Enomoto-Iwamoto, M, Iwamoto, M, Mukudai, Y, Kawakami, Y, Nohno, T, Higuchi, Y, Takemoto, S, Ohuchi, H, Noji, S and Kurisu, K (1998) Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. J. Cell Biol. 140:409-18

Abstract

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.

Links

PubMed PMC2132568

Keywords

Animals; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins/physiology; Cell Differentiation; Cell Division; Chick Embryo; Chondrocytes/cytology; Collagen/metabolism; Phenotype; Protein-Serine-Threonine Kinases/metabolism; Proteoglycans/metabolism; Receptors, Cell Surface/metabolism; Receptors, Growth Factor/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CHICK:F1NTD3

involved_in

GO:0002063: chondrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:F1NTD3

located_in

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:F1NTD3

involved_in

GO:1902731: negative regulation of chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:F1P3H0

NOT|involved_in

GO:0002063: chondrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:F1P3H0

located_in

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:F1P3H0

NOT|involved_in

GO:0035988: chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:BMR1B

located_in

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMPR2

located_in

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:Q90754

located_in

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:BMR1B

involved_in

GO:0002063: chondrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:BMR1B

involved_in

GO:1902731: negative regulation of chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:BMR1B

part_of

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

CHICK:Q90754

NOT|involved_in

GO:0035988: chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q90754

NOT|involved_in

GO:0002063: chondrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q90754

part_of

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMPR2

involved_in

GO:1902731: negative regulation of chondrocyte proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BMPR2

involved_in

GO:0030509: BMP signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BMPR2

involved_in

GO:0002063: chondrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BMPR2

part_of

GO:0044214: spanning component of plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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