Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage

E. A. Parker, A. Hegde, M. Buckley, K. M. Barnes, Jeffrey Baron, O. Nilsson

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Previous studies of the GH-IGF system gene expression in growth plate using immunohistochemistry and in situ hybridization have yielded conflicting results. We therefore studied the spatial and temporal patterns of mRNA expression of the GH-IGF system in the rat proximal tibial growth plate quantitatively. Growth plates were microdissected into individual zones. RNA was extracted, reverse transcribed and analyzed by real-time PCR. In 1-week-old animals, IGF-I mRNA expression was minimal in growth plate compared with perichondrium, metaphyseal bone, muscle, and liver (70-, 130-, 215-, and 400-fold less). In contrast, IGF-II mRNA was expressed at higher levels than in bone and liver (65- and 2-fold). IGF-II expression was higher in the proliferative and resting zones compared with the hypertrophic zone (P<0.001). GH receptor and type 1 and 2 IGF receptors were expressed throughout the growth plate. Expression of IGF-binding proteins (IGFBPs)-1 through -6 mRNA was low throughout the growth plate compared with perichondrium and bone. With increasing age (3-, 6-, 9-, and 12-week castrated rats), IGF-I mRNA levels increased in the proliferative zone (PZ) but remained at least tenfold lower than levels in perichondrium and bone. IGF-II mRNA decreased dramatically in PZ (780-fold; P<0.001) whereas, type 2 IGF receptor and IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 increased significantly with age in growth plate and/or surrounding perichondrium and bone. These data suggest that IGF-I protein in the growth plate is not produced primarily by the chondrocytes themselves. Instead, it derives from surrounding perichondrium and bone. In addition, the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalJournal of Endocrinology
Volume194
Issue number1
DOIs
StatePublished - Jul 2007

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Growth Plate
Cartilage
Gene Expression
Insulin-Like Growth Factor II
IGF Type 2 Receptor
Bone and Bones
Messenger RNA
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor
Insulin-Like Growth Factor Binding Protein 3
Liver
Chondrocytes
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Immunohistochemistry
RNA

ASJC Scopus subject areas

  • Endocrinology

Cite this

Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. / Parker, E. A.; Hegde, A.; Buckley, M.; Barnes, K. M.; Baron, Jeffrey; Nilsson, O.

In: Journal of Endocrinology, Vol. 194, No. 1, 07.2007, p. 31-40.

Research output: Contribution to journalArticle

Parker, E. A. ; Hegde, A. ; Buckley, M. ; Barnes, K. M. ; Baron, Jeffrey ; Nilsson, O. / Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. In: Journal of Endocrinology. 2007 ; Vol. 194, No. 1. pp. 31-40.
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