Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes

Stephen Trippel, S. D. Chernausek, J. J. Van Wijk, A. C. Moses, H. J. Mankin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The chondrocytes of the epiphyseal growth plate are the presumed target cells for hormones regulating skeletal growth. The somatomedins, a family of low molecular weight peptides, are thought to play a stimulatory role in this regulation. The cellular actions of the somatomedins are themselves determined by binding to specific receptors on target cells. Previous studies have characterized a specific receptor for somatomedin-C (Sm-C) or insulin-like growth factor I (IGF-I) on bovine growth plate chondrocytes (GPCs). We now report the characterization of a second type of somatomedin receptor on these cells that is more specific for another class of somatomedin represented by multiplication-stimulating activity (MSA) or rat insulin-like growth factor II (rIGF-II). Binding of [125I]MSA/rIGF-II to isolated GPCs was time dependent and saturable. Unlabeled M(r) 7,100 MSA/rIGF-II and Sm-C/IGF-I were approximately equipotent in competing with [125I]MSA/rIGF-II for binding, while M(r) 8,600 MSA/rIGF-II was an order of magnitude less potent. Low levels of competition by insulin appeared in some studies at concentrations of 10-7 M and higher, suggesting displacement of [125I]MSA/rIGF-II binding to the Sm-C/IGF-I receptor. In affinity-labeling studies, [125I]Sm-C/IGF-I labeled a complex of M(r) > 300,000 (unreduced) and of M(r) 140,000 (reduced), consistent with a type I somatomedin receptor composed of disulfide-linked subunits. [125I]MSA/rIGF-II labeled a M(r) 240,000 moiety (unreduced) and M(r) 260,000 (reduced), consistent with a type II somatomedin receptor. Both affinity-labeling and kinetic data revealed cross-binding of MSA/rIGF-II and insulin with the type I receptor and of Sm-C/IGF-I with the type II receptor. In contrast, the type II receptor did not recognize insulin. These data suggest a complex pattern of graded specificity of these receptors for their ligands. These data are consistent with the hypothesis that IGF-II as well as Sm-C/IGF-I participate in the stimulation of skeletal growth.

Original languageEnglish (US)
Pages (from-to)817-826
Number of pages10
JournalJournal of Orthopaedic Research
Volume6
Issue number6
StatePublished - 1988
Externally publishedYes

Fingerprint

Somatomedin Receptors
Growth Plate
Chondrocytes
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Somatomedins
Insulin
IGF Type 1 Receptor
rat insulin-like growth factor II
Growth
Disulfides
Molecular Weight

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Trippel, S., Chernausek, S. D., Van Wijk, J. J., Moses, A. C., & Mankin, H. J. (1988). Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes. Journal of Orthopaedic Research, 6(6), 817-826.

Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes. / Trippel, Stephen; Chernausek, S. D.; Van Wijk, J. J.; Moses, A. C.; Mankin, H. J.

In: Journal of Orthopaedic Research, Vol. 6, No. 6, 1988, p. 817-826.

Research output: Contribution to journalArticle

Trippel, S, Chernausek, SD, Van Wijk, JJ, Moses, AC & Mankin, HJ 1988, 'Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes', Journal of Orthopaedic Research, vol. 6, no. 6, pp. 817-826.
Trippel, Stephen ; Chernausek, S. D. ; Van Wijk, J. J. ; Moses, A. C. ; Mankin, H. J. / Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes. In: Journal of Orthopaedic Research. 1988 ; Vol. 6, No. 6. pp. 817-826.
@article{89dd80aaec484ee3902f3fa349a59b1d,
title = "Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes",
abstract = "The chondrocytes of the epiphyseal growth plate are the presumed target cells for hormones regulating skeletal growth. The somatomedins, a family of low molecular weight peptides, are thought to play a stimulatory role in this regulation. The cellular actions of the somatomedins are themselves determined by binding to specific receptors on target cells. Previous studies have characterized a specific receptor for somatomedin-C (Sm-C) or insulin-like growth factor I (IGF-I) on bovine growth plate chondrocytes (GPCs). We now report the characterization of a second type of somatomedin receptor on these cells that is more specific for another class of somatomedin represented by multiplication-stimulating activity (MSA) or rat insulin-like growth factor II (rIGF-II). Binding of [125I]MSA/rIGF-II to isolated GPCs was time dependent and saturable. Unlabeled M(r) 7,100 MSA/rIGF-II and Sm-C/IGF-I were approximately equipotent in competing with [125I]MSA/rIGF-II for binding, while M(r) 8,600 MSA/rIGF-II was an order of magnitude less potent. Low levels of competition by insulin appeared in some studies at concentrations of 10-7 M and higher, suggesting displacement of [125I]MSA/rIGF-II binding to the Sm-C/IGF-I receptor. In affinity-labeling studies, [125I]Sm-C/IGF-I labeled a complex of M(r) > 300,000 (unreduced) and of M(r) 140,000 (reduced), consistent with a type I somatomedin receptor composed of disulfide-linked subunits. [125I]MSA/rIGF-II labeled a M(r) 240,000 moiety (unreduced) and M(r) 260,000 (reduced), consistent with a type II somatomedin receptor. Both affinity-labeling and kinetic data revealed cross-binding of MSA/rIGF-II and insulin with the type I receptor and of Sm-C/IGF-I with the type II receptor. In contrast, the type II receptor did not recognize insulin. These data suggest a complex pattern of graded specificity of these receptors for their ligands. These data are consistent with the hypothesis that IGF-II as well as Sm-C/IGF-I participate in the stimulation of skeletal growth.",
author = "Stephen Trippel and Chernausek, {S. D.} and {Van Wijk}, {J. J.} and Moses, {A. C.} and Mankin, {H. J.}",
year = "1988",
language = "English (US)",
volume = "6",
pages = "817--826",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes

AU - Trippel, Stephen

AU - Chernausek, S. D.

AU - Van Wijk, J. J.

AU - Moses, A. C.

AU - Mankin, H. J.

PY - 1988

Y1 - 1988

N2 - The chondrocytes of the epiphyseal growth plate are the presumed target cells for hormones regulating skeletal growth. The somatomedins, a family of low molecular weight peptides, are thought to play a stimulatory role in this regulation. The cellular actions of the somatomedins are themselves determined by binding to specific receptors on target cells. Previous studies have characterized a specific receptor for somatomedin-C (Sm-C) or insulin-like growth factor I (IGF-I) on bovine growth plate chondrocytes (GPCs). We now report the characterization of a second type of somatomedin receptor on these cells that is more specific for another class of somatomedin represented by multiplication-stimulating activity (MSA) or rat insulin-like growth factor II (rIGF-II). Binding of [125I]MSA/rIGF-II to isolated GPCs was time dependent and saturable. Unlabeled M(r) 7,100 MSA/rIGF-II and Sm-C/IGF-I were approximately equipotent in competing with [125I]MSA/rIGF-II for binding, while M(r) 8,600 MSA/rIGF-II was an order of magnitude less potent. Low levels of competition by insulin appeared in some studies at concentrations of 10-7 M and higher, suggesting displacement of [125I]MSA/rIGF-II binding to the Sm-C/IGF-I receptor. In affinity-labeling studies, [125I]Sm-C/IGF-I labeled a complex of M(r) > 300,000 (unreduced) and of M(r) 140,000 (reduced), consistent with a type I somatomedin receptor composed of disulfide-linked subunits. [125I]MSA/rIGF-II labeled a M(r) 240,000 moiety (unreduced) and M(r) 260,000 (reduced), consistent with a type II somatomedin receptor. Both affinity-labeling and kinetic data revealed cross-binding of MSA/rIGF-II and insulin with the type I receptor and of Sm-C/IGF-I with the type II receptor. In contrast, the type II receptor did not recognize insulin. These data suggest a complex pattern of graded specificity of these receptors for their ligands. These data are consistent with the hypothesis that IGF-II as well as Sm-C/IGF-I participate in the stimulation of skeletal growth.

AB - The chondrocytes of the epiphyseal growth plate are the presumed target cells for hormones regulating skeletal growth. The somatomedins, a family of low molecular weight peptides, are thought to play a stimulatory role in this regulation. The cellular actions of the somatomedins are themselves determined by binding to specific receptors on target cells. Previous studies have characterized a specific receptor for somatomedin-C (Sm-C) or insulin-like growth factor I (IGF-I) on bovine growth plate chondrocytes (GPCs). We now report the characterization of a second type of somatomedin receptor on these cells that is more specific for another class of somatomedin represented by multiplication-stimulating activity (MSA) or rat insulin-like growth factor II (rIGF-II). Binding of [125I]MSA/rIGF-II to isolated GPCs was time dependent and saturable. Unlabeled M(r) 7,100 MSA/rIGF-II and Sm-C/IGF-I were approximately equipotent in competing with [125I]MSA/rIGF-II for binding, while M(r) 8,600 MSA/rIGF-II was an order of magnitude less potent. Low levels of competition by insulin appeared in some studies at concentrations of 10-7 M and higher, suggesting displacement of [125I]MSA/rIGF-II binding to the Sm-C/IGF-I receptor. In affinity-labeling studies, [125I]Sm-C/IGF-I labeled a complex of M(r) > 300,000 (unreduced) and of M(r) 140,000 (reduced), consistent with a type I somatomedin receptor composed of disulfide-linked subunits. [125I]MSA/rIGF-II labeled a M(r) 240,000 moiety (unreduced) and M(r) 260,000 (reduced), consistent with a type II somatomedin receptor. Both affinity-labeling and kinetic data revealed cross-binding of MSA/rIGF-II and insulin with the type I receptor and of Sm-C/IGF-I with the type II receptor. In contrast, the type II receptor did not recognize insulin. These data suggest a complex pattern of graded specificity of these receptors for their ligands. These data are consistent with the hypothesis that IGF-II as well as Sm-C/IGF-I participate in the stimulation of skeletal growth.

UR - http://www.scopus.com/inward/record.url?scp=0023816588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023816588&partnerID=8YFLogxK

M3 - Article

C2 - 2971791

AN - SCOPUS:0023816588

VL - 6

SP - 817

EP - 826

JO - Journal of Orthopaedic Research

JF - Journal of Orthopaedic Research

SN - 0736-0266

IS - 6

ER -