Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I

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Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I. / Kiepe, Daniela; Van Der Pas, Anke; Ciarmatori, Sonia; Ständker, Ludger; Schütt, Burkhardt; Hoeflich, Andreas; Hügel, Ulrike; Oh, Jun; Tönshoff, Burkhard.

in: ENDOCRINOLOGY, Jahrgang 149, Nr. 10, 10.2008, S. 4901-11.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{db2f49dfa5b74bc5ae455c0bb4cab380,
title = "Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I",
abstract = "The IGF/IGF binding protein (IGFBP) system is an important component in the hormonal regulation of longitudinal growth. Evidence from in vitro studies indicates that IGFBPs may have IGF-independent effects. We analyzed the biological activity of intact IGFBP-2 and defined carboxy-terminal IGFBP-2 fragments isolated from human hemofiltrate in two cell culture systems of the growth plate: rat growth plate chondrocytes in primary culture and the mesenchymal chondrogenic cell line RCJ3.1C5.18. The IGFBP-2 fragments IGFBP-2(167-279), IGFBP-2(167-289), and IGFBP-2(104-289) exerted a strong (2- to 3-fold) mitogenic effect on growth plate chondrocytes, which was comparable with IGF-I in equimolar concentrations (7.8 nm) but was not mediated through the type 1 IGF receptor. In a dose-response experiment, the most effective concentration of IGFBP-2(104-289) for the stimulation of cell proliferation was 10 nm. This biological activity of IGFBP-2 fragments was associated with cell membrane binding, demonstrated by Western blot analysis of fractionated cell lysates and immunohistochemistry. Whereas intact IGFBP-2 did not modulate chondrocyte proliferation, partially reduced (by dithiothreitol) full-length IGFBP-2 stimulated cell proliferation to a comparable extent (3.4-fold) as carboxy-terminal IGFBP-2 fragments. The mitogenic activity of these IGFBP-2 fragments and of partially reduced full-length IGFBP-2 was mediated through the use of the MAPK/ERK 1/2. These data imply a novel role of naturally occurring IGFBP-2 fragments for the endocrine and paracrine/autocrine regulation of longitudinal growth.",
keywords = "Animals, Cell Division/drug effects, Cell Membrane/metabolism, Cells, Cultured, Chondrocytes/cytology, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases/metabolism, Focal Adhesion Protein-Tyrosine Kinases/metabolism, Growth Plate/cytology, Humans, Insulin-Like Growth Factor Binding Protein 2/genetics, Insulin-Like Growth Factor I/metabolism, MAP Kinase Signaling System/drug effects, Mitogen-Activated Protein Kinases/metabolism, Mitogens/pharmacology, Peptide Fragments/genetics, Rats",
author = "Daniela Kiepe and {Van Der Pas}, Anke and Sonia Ciarmatori and Ludger St{\"a}ndker and Burkhardt Sch{\"u}tt and Andreas Hoeflich and Ulrike H{\"u}gel and Jun Oh and Burkhard T{\"o}nshoff",
year = "2008",
month = oct,
doi = "10.1210/en.2007-1395",
language = "English",
volume = "149",
pages = "4901--11",
journal = "ENDOCRINOLOGY",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "10",

}

RIS

TY - JOUR

T1 - Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I

AU - Kiepe, Daniela

AU - Van Der Pas, Anke

AU - Ciarmatori, Sonia

AU - Ständker, Ludger

AU - Schütt, Burkhardt

AU - Hoeflich, Andreas

AU - Hügel, Ulrike

AU - Oh, Jun

AU - Tönshoff, Burkhard

PY - 2008/10

Y1 - 2008/10

N2 - The IGF/IGF binding protein (IGFBP) system is an important component in the hormonal regulation of longitudinal growth. Evidence from in vitro studies indicates that IGFBPs may have IGF-independent effects. We analyzed the biological activity of intact IGFBP-2 and defined carboxy-terminal IGFBP-2 fragments isolated from human hemofiltrate in two cell culture systems of the growth plate: rat growth plate chondrocytes in primary culture and the mesenchymal chondrogenic cell line RCJ3.1C5.18. The IGFBP-2 fragments IGFBP-2(167-279), IGFBP-2(167-289), and IGFBP-2(104-289) exerted a strong (2- to 3-fold) mitogenic effect on growth plate chondrocytes, which was comparable with IGF-I in equimolar concentrations (7.8 nm) but was not mediated through the type 1 IGF receptor. In a dose-response experiment, the most effective concentration of IGFBP-2(104-289) for the stimulation of cell proliferation was 10 nm. This biological activity of IGFBP-2 fragments was associated with cell membrane binding, demonstrated by Western blot analysis of fractionated cell lysates and immunohistochemistry. Whereas intact IGFBP-2 did not modulate chondrocyte proliferation, partially reduced (by dithiothreitol) full-length IGFBP-2 stimulated cell proliferation to a comparable extent (3.4-fold) as carboxy-terminal IGFBP-2 fragments. The mitogenic activity of these IGFBP-2 fragments and of partially reduced full-length IGFBP-2 was mediated through the use of the MAPK/ERK 1/2. These data imply a novel role of naturally occurring IGFBP-2 fragments for the endocrine and paracrine/autocrine regulation of longitudinal growth.

AB - The IGF/IGF binding protein (IGFBP) system is an important component in the hormonal regulation of longitudinal growth. Evidence from in vitro studies indicates that IGFBPs may have IGF-independent effects. We analyzed the biological activity of intact IGFBP-2 and defined carboxy-terminal IGFBP-2 fragments isolated from human hemofiltrate in two cell culture systems of the growth plate: rat growth plate chondrocytes in primary culture and the mesenchymal chondrogenic cell line RCJ3.1C5.18. The IGFBP-2 fragments IGFBP-2(167-279), IGFBP-2(167-289), and IGFBP-2(104-289) exerted a strong (2- to 3-fold) mitogenic effect on growth plate chondrocytes, which was comparable with IGF-I in equimolar concentrations (7.8 nm) but was not mediated through the type 1 IGF receptor. In a dose-response experiment, the most effective concentration of IGFBP-2(104-289) for the stimulation of cell proliferation was 10 nm. This biological activity of IGFBP-2 fragments was associated with cell membrane binding, demonstrated by Western blot analysis of fractionated cell lysates and immunohistochemistry. Whereas intact IGFBP-2 did not modulate chondrocyte proliferation, partially reduced (by dithiothreitol) full-length IGFBP-2 stimulated cell proliferation to a comparable extent (3.4-fold) as carboxy-terminal IGFBP-2 fragments. The mitogenic activity of these IGFBP-2 fragments and of partially reduced full-length IGFBP-2 was mediated through the use of the MAPK/ERK 1/2. These data imply a novel role of naturally occurring IGFBP-2 fragments for the endocrine and paracrine/autocrine regulation of longitudinal growth.

KW - Animals

KW - Cell Division/drug effects

KW - Cell Membrane/metabolism

KW - Cells, Cultured

KW - Chondrocytes/cytology

KW - Dose-Response Relationship, Drug

KW - Extracellular Signal-Regulated MAP Kinases/metabolism

KW - Focal Adhesion Protein-Tyrosine Kinases/metabolism

KW - Growth Plate/cytology

KW - Humans

KW - Insulin-Like Growth Factor Binding Protein 2/genetics

KW - Insulin-Like Growth Factor I/metabolism

KW - MAP Kinase Signaling System/drug effects

KW - Mitogen-Activated Protein Kinases/metabolism

KW - Mitogens/pharmacology

KW - Peptide Fragments/genetics

KW - Rats

U2 - 10.1210/en.2007-1395

DO - 10.1210/en.2007-1395

M3 - SCORING: Journal article

C2 - 18556354

VL - 149

SP - 4901

EP - 4911

JO - ENDOCRINOLOGY

JF - ENDOCRINOLOGY

SN - 0013-7227

IS - 10

ER -