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Insulin‐like growth factor binding protein–4 inhibits both basal and IGF‐mediated chick pelvic cartilage growth in vitro
Author(s) -
Schiltz Patric M.,
Mohan Subburaman,
Baylink David J.
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080402
Subject(s) - cartilage , insulin like growth factor binding protein , in vitro , growth factor , somatomedin , endocrinology , medicine , radioimmunoassay , insulin like growth factor , thymidine , biology , insulin like growth factor 2 , basal (medicine) , insulin , receptor , anatomy , biochemistry
This laboratory has purified a unique insulin‐like growth factor binding protein (IGFBP‐4) that was previously demonstrated to be inhibitory to bone cell proliferation. In this study, the hypothesis that IGFBP‐4 is inhibitory to insulin‐like growth factor (IGF) actions on cartilage was tested using the pelvic cartilages of 10‐day‐old chick embryos as an in vitro model system. Pelvic leaflets were incubated in serum‐free medium for 18 h with effectors (BSA, IGF‐I, IGF‐II, IGFBP‐4, or a combination of IGF and IGFBP‐4). After the first 8 h, 1.5 μCi [ 3 H]thymidine per well was added. Cartilage growth was assayed by TCA‐insoluble [ 3 H]thymidine incorporation into DNA. Additional experiments were conducted under similar conditions to assess the actions of the effectors on cartilage dry weight over a 72 h time period. In separate experiments, serum‐free medium conditioned by chick pelvic cartilages for 72 h was assayed for IGF‐II by radioreceptorassay, IGF‐I by radioimmunoassay, and IGFBP by western ligand analysis. Exogenous IGF addition increased [ 3 H]thymidine incorporation and dry weight of cartilages compared to controls. IGFBP‐4 decreased both parameters in basal cartilage growth and also inhibited IGF‐mediated cartilage growth. Pelvic cartilages secreted in vitro both IGF‐I and IGF‐II and a 32–34 kD IGFBP. In conclusion, the IGFs are stimulatory to cartilage growth in vitro and embryonic chick cartilage in vitro produces both IGF‐I and II as well as an IGFBP. Exogenous IGFBP‐4 inhibits both the basal and IGF‐mediated growth of chick cartilage, suggesting that IGFBP‐4 acts to downregulate the growth‐promoting effects of IGFs on cartilage growth.