A novel insulin-like growth factor (IGF)-independent role for IGF binding protein-3 in mesenchymal chondroprogenitor cell apoptosis
| Autor: | Caroline K. Buckway, William A. Horton, Ron G. Rosenfeld, Francesco Chiarelli, Charles T. Roberts, Lynda O'Rear, Anna Spagnoli, Vivian Hwa, Lara Longobardi, Monica Torello |
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| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Cellular differentiation Binding protein Stem Cells Mesenchymal stem cell Apoptosis Cell Differentiation Transfection Biology Chondrogenesis Chondrocyte Cell Line Mesoderm Insulin-like growth factor Endocrinology medicine.anatomical_structure Chondrocytes Insulin-Like Growth Factor Binding Protein 3 Cell culture Somatomedins Internal medicine medicine Animals |
| Zdroj: | Endocrinology. 144(5) |
| ISSN: | 0013-7227 |
| Popis: | Chondrogenesis results from the condensation of mesenchymal chondroprogenitor cells (MCC) that proliferate and differentiate into chondrocytes. We have previously shown that IGF binding protein (IGFBP)-3 has an IGF-independent antiproliferative effect in MCC. The current study evaluates the IGF-independent apoptotic effect of IGFBP-3 on MCC to modulate chondrocyte differentiation. We employed the RCJ3.1C5.18 chondrogenic cell line, which in culture progresses from MCC to differentiated chondrocytes; cells do not express IGFs or IGFBP-3. We also used IGFBP-3 mutants with decreased (I56 substituted to G56; L80 and L81 to G80G81) or abolished binding for IGFs (I56, L80, and L81 to G56G80G81). MCC transfected with IGFBP-3 detached, changed their phenotype, and underwent apoptosis. A maximal IGFBP-3 apoptotic effect was observed 24 h after transfection (463 ± 73% of controls; P < 0.001). Remarkably, IGFBP-3 mutants had similar effects, demonstrating that the IGFBP-3 apoptotic action was clearly IGF independent. In addition, treatment with IGFBP-3 in serum-free conditions resulted in a significant increase of apoptosis (173 ± 23% of controls; P < 0.05). Moreover, this apoptotic effect was selective for MCC, resulting in a selective reduction of chondrocytic nodules and a significant decrease in type II collagen expression and proteoglycan synthesis. In summary, we have identified a novel IGF-independent role for IGFBP-3 in the modulation of chondrocyte differentiation. |
| Databáze: | OpenAIRE |
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