Expression levels of insulin receptor substrate-1 modulate the osteoblastic differentiation of mesenchymal stem cells and osteosarcoma cells.
Growth Factors
; 32(1): 41-52, 2014 Feb.
Article
in En
| MEDLINE
| ID: mdl-24438070
ABSTRACT
The insulin-like growth factor-1 system, including its critical mediator insulin receptor substrate-1 (IRS-1), is involved in regulating osteosarcoma (OS) cell proliferation or differentiation. The aim of this study is to define the role of IRS-1 in OS cells by assessing the contribution of IRS-1 in the differentiation of human and murine OS cell lines and mouse mesenchymal stem cells (MSCs) and found that the basal level of IRS-1 is important for the initiation of differentiation. Both down-regulation and over-expression of IRS-1 inhibited osteoblastic differentiation. In vivo studies showed that OS cells over-expressing IRS-1 have increased metastatic potential and tumor growth. The proteasome inhibitor MG-132 led to an increase in IRS-1 protein level that inhibited osteoblastic differentiation, suggesting a role for proteasomal regulation in maintaining the appropriate expression level of IRS-1. Thus, precise regulation of IRS-1 expression level is critical for determining the differentiating capacity of MSCs and OS cells, and that derangement of IRS-1 levels can be a critical step in OS transformation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoblasts
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Insulin-Like Growth Factor I
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Osteosarcoma
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Insulin Receptor Substrate Proteins
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Mesenchymal Stem Cells
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Growth Factors
Journal subject:
BIOLOGIA
Year:
2014
Type:
Article
Affiliation country:
Italy