+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Igf-I extends the chondrogenic potential of human articular chondrocytes in vitro: molecular association between Sox9 and Erk1/2.

      Biochemical Pharmacology

      Cell Differentiation, Biological Markers, metabolism, Cartilage, Articular, drug effects, ultrastructure, physiology, Cells, Cultured, Chondrocytes, Collagen Type II, High Mobility Group Proteins, Humans, Insulin-Like Growth Factor I, pharmacology, Microscopy, Electron, Transmission, Microscopy, Immunoelectron, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, SOX9 Transcription Factor, Transcription Factors

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Expansion of articular chondrocytes in monolayer culture leads to loss of the unique chondrocyte phenotype and the cells' redifferentiation capacity. Dedifferentiation of chondrocytes in monolayer culture is a challenging problem for autologous chondrocyte transplantation (ACT). It is well established that Igf-I exerts positive anabolic effects on chondrocytes in vivo and in vitro. Accordingly, in this study, we examined whether the anabolic insulin-like growth factor-I (Igf-I) is capable of extending the chondrogenic potential of dedifferentiated chondrocytes in vitro. Chondrocyte monolayers were cultured up to 10 passages. At each passage chondrocytes were stimulated with Igf-I (10ng/ml) and introduced to high-density cultures for up to 7 days. Expression of collagen type II, cartilage-specific proteoglycans, activated caspase-3, integrin beta1, extracellular signal-regulated kinase (Erk) and Sox9 was examined by Western blotting, immunoprecipitation and immunomorphological techniques. Monolayer chondrocytes rapidly lost their differentiated phenotype. When introduced to high-density cultures, only chondrocytes from P1-P4 redifferentiated. In contrast, Igf-I treated cells from P1 up to P7 redifferentiated and formed cartilage-like tissue in high-density culture. P8-P10 cells exhibited apoptotic alterations and produced significantly less matrix. Igf-I markedly increased expression of integrin beta1, Erk and Sox9. Immunoprecipitation revealed that phosphorylated Erk1/2 physically interacts with Sox9 in chondrocyte nuclei, suggesting a previously unreported functional association which was markedly enhanced by Igf-I. Treatment of chondrocyte cultures with Igf-I stabilizes chondrogenic potential, stimulates Sox9 and promotes molecular interactions between Erk and Sox9. These effects appear to be regulated by the integrin/MAPK signaling pathways.

          Related collections

          Author and article information



          Comment on this article