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Signaling mechanisms leading to the regulation of differentiation and apoptosis of articular chondrocytes by insulin-like growth factor-1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chun, Jang-Soo |
| Copyright Year | 2003 |
| Abstract | Cartilage development is initiated by the differentiation of mesenchymal cells into chondrocytes. Differentiated chondrocytes in articular cartilage undergo dedifferentiation and apoptosis during arthritis, in which NO production plays a critical role. Here, we investigated the roles and mechanisms of action of insulin-like growth factor-1 (IGF-1) in the chondrogenesis of mesenchymal cells and the maintenance and survival of differentiated articular chondrocytes. IGF-1 induced chondrogenesis of limb bud mesenchymal cells during micromass culture through the activation of phosphatidylinositol 3-kinase (PI3K) and Akt. PI3K activation is required for the activation of protein kinase C (PKC)-alpha and p38 kinase and inhibition of ERK1/2. These events are necessary for chondrogenesis. The growth factor additionally blocked NO-induced dedifferentiation and apoptosis of primary culture articular chondrocytes. NO production in chondrocytes induced down-regulation of PI3K and Akt activities, which was blocked by IGF-1 treatment. Stimulation of PI3K by IGF-1 resulted in blockage of NO-induced activation of p38 kinase and ERK1/2 and inhibition of PKCalpha and PKCzeta, which in turn suppressed dedifferentiation and apoptosis. Our results collectively indicate that IGF-1 regulates differentiation, maintenance of the differentiated phenotype, and apoptosis of articular chondrocytes via a PI3K pathway that modulates ERK, p38 kinase, and PKC signaling. |
| Starting Page | 2643 |
| Ending Page | 2653 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/early/2003/07/09/jbc.M304857200.full.pdf |
| PubMed reference number | 12853454v1 |
| Volume Number | 278 |
| Issue Number | 38 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase Anaplasia Apoptosis Arthritis Bud - CHV concept Cell Differentiation process Chondrocyte Chondrogenesis Down-Regulation Growth Factor Limb Buds Protein Kinase C Protein Kinases Proto-Oncogene Proteins c-akt Somatomedin-C measurement Somatomedins Structure of articular cartilage |
| Content Type | Text |
| Resource Type | Article |
