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The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I-mediated growth of chick embryo pelvic cartilage in vitro.

Publication ,  Journal Article
Burch, WM; Correa, J; Shively, JE; Powell, DR
Published in: J Clin Endocrinol Metab
January 1990

Insulin-like growth factor (IGF)-I stimulates the growth of many tissues, including growth plate cartilage. However, the role of IGF-binding proteins in the growth process is controversial. We purified a 25-kDa IGF-binding protein (BP-25) from amniotic fluid. We tested the effect of this BP-25 preparation on both basal and IGF-I-stimulated growth of chick embryo pelvic cartilages maintained in serum-free organ culture. Cartilage wet weight was 4.1 +/- 0.3 mg/cartilage initially; after 3 days, BP-25 inhibited both basal and IGF-I-stimulated growth. Control cartilages weighed 7.4 +/- 0.7 mg/cartilage, while those incubated with 100 nM BP-25 weighed 5.8 +/- 0.5 mg/cartilage (P less than 0.001 vs. control); BP-25 concentrations as low as 0.2 nM significantly inhibited basal cartilage growth. Cartilages incubated with 1.25 nM IGF-I weighed 10.4 +/- 0.8 mg/cartilage (P less than 0.001 vs. control), while those incubated with both 100 nM BP-25 and 1.25 nM IGF-I weighed 8.1 +/- 0.5 mg/cartilage (P less than 0.001 vs. cartilage incubated with IGF-I alone); BP-25 concentrations as low as 0.4 nM significantly inhibited IGF-I-stimulated cartilage growth. BP-25 also inhibited basal and IGF-I-stimulated increases in cartilage dry weight, [3H]thymidine incorporation into DNA, and 35SO4 incorporation into proteoglycan. A second BP-25 preparation, which in the presence of 1% platelet-poor plasma acts synergistically with IGF-I to stimulate DNA synthesis and cell replication of fibroblasts and smooth muscle cells in tissue culture, inhibited IGF-I-stimulated cartilage growth to the same degree as did our BP-25 preparation. In separate experiments, proteins present in serum-free medium conditioned for 3 days by chick cartilages were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and incubated with [125I]IGF-I. This medium was found to contain two IGF-binding proteins; one appeared to be the chick equivalent of BP-25, while the other had a molecular mass similar to that of a poorly characterized human 34-kDa IGF-binding protein. We conclude that purified BP-25 inhibits the growth of chick embryo pelvic cartilage in our serum-free organ culture system. Since conditioned medium from these cartilages contains both IGF-I-like peptides and IGF-binding proteins such as BP-25, we suggest that the IGF-binding proteins present may act to down-regulate the growth-promoting effects of the local IGF peptides.

Duke Scholars

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

January 1990

Volume

70

Issue

1

Start / End Page

173 / 180

Location

United States

Related Subject Headings

  • Thymidine
  • Somatomedins
  • Peptides
  • Pelvic Bones
  • Organ Size
  • Organ Culture Techniques
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Proteins
  • Endocrinology & Metabolism
  • Down-Regulation
 

Citation

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Burch, W. M., Correa, J., Shively, J. E., & Powell, D. R. (1990). The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I-mediated growth of chick embryo pelvic cartilage in vitro. J Clin Endocrinol Metab, 70(1), 173–180. https://doi.org/10.1210/jcem-70-1-173
Burch, W. M., J. Correa, J. E. Shively, and D. R. Powell. “The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I-mediated growth of chick embryo pelvic cartilage in vitro.J Clin Endocrinol Metab 70, no. 1 (January 1990): 173–80. https://doi.org/10.1210/jcem-70-1-173.
Burch, W. M., et al. “The 25-kilodalton insulin-like growth factor (IGF)-binding protein inhibits both basal and IGF-I-mediated growth of chick embryo pelvic cartilage in vitro.J Clin Endocrinol Metab, vol. 70, no. 1, Jan. 1990, pp. 173–80. Pubmed, doi:10.1210/jcem-70-1-173.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

January 1990

Volume

70

Issue

1

Start / End Page

173 / 180

Location

United States

Related Subject Headings

  • Thymidine
  • Somatomedins
  • Peptides
  • Pelvic Bones
  • Organ Size
  • Organ Culture Techniques
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Proteins
  • Endocrinology & Metabolism
  • Down-Regulation