Insulin-like growth factor (IGF)-I stimulates cell proliferation and induces IGF binding protein (IGFBP)-3 and IGFBP-5 gene expression in cultured growth plate chondrocytes via distinct signaling pathways
| Autor: | Sonia Ciarmatori, Andreas Hoeflich, Eckhard Wolf, Burkhard Tönshoff, Daniela Kiepe |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Transcription Genetic medicine.medical_treatment Gene Expression Biology Insulin-like growth factor-binding protein Chondrocyte Rats Sprague-Dawley Insulin-like growth factor Phosphatidylinositol 3-Kinases Endocrinology Chondrocytes Internal medicine Gene expression medicine Animals Humans Growth Plate RNA Messenger Insulin-Like Growth Factor I Cells Cultured Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Cell growth Molecular biology Recombinant Proteins Rats medicine.anatomical_structure Insulin-Like Growth Factor Binding Protein 3 Cell culture Culture Media Conditioned biology.protein Signal transduction Insulin-Like Growth Factor Binding Protein 5 hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Endocrinology. 146(7) |
| ISSN: | 0013-7227 |
| Popis: | The bioactivity of IGF-I in the cellular microenvironment is modulated by both inhibitory and stimulatory IGF binding proteins (IGFBPs), whose production is partially under control of IGF-I. However, little is known on the IGF-mediated regulation of these IGFBPs in the growth plate. We therefore studied the effect of IGF-I on IGFBP synthesis and the involved intracellular signaling pathways in two cell culture models of rat growth plate chondrocytes. In growth plate chondrocytes in primary culture, incubation with IGF-I increased the concentrations of IGFBP-3 and IGFBP-5 in conditioned cell culture medium in a dose- and time-dependent manner. Coincubation of IGF-I with specific inhibitors of the p42/44 MAPK pathway (PD098059 or U0126) completely abolished the stimulatory effect of IGF-I on IGFBP-3 mRNA expression but did not affect increased IGFBP-5 mRNA levels. In contrast, inhibition of the phosphatidylinositol-3 kinase signaling pathway by LY294002 abrogated both IGF-I-stimulated IGFBP-3 and -5 mRNA expression. Comparable results regarding IGFBP-5 were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does not express IGFBP-3. The IGF-I-induced IGFBP-5 gene expression required de novo mRNA transcription and de novo protein synthesis. These data suggest that IGF-I modulates its activity in cultured rat growth plate chondrocytes by the synthesis of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins. The finding that IGF-I uses different and only partially overlapping intracellular signaling pathways for the regulation of two IGFBPs with opposing biological functions might be important for the modulation of IGF bioactivity in the cellular microenvironment. |
| Databáze: | OpenAIRE |
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