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
Standard
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, Vol. 149, No. 10, 10.2008, p. 4901-11.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
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 -