COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways
| Autor: | Seong-Kyu Han, Sung-Ho Kook, Cheol-Hyeon Bae, Young-Kwon Seo, Eui-Sic Cho, Kyung-Yeol Lee, Jae-Won Hwang, Jungkee Kwon, Jeong-Chae Lee, Shin-Saeng Lim, Young-Hoon Lee |
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| Rok vydání: | 2014 |
| Předmět: |
musculoskeletal diseases
MAPK/ERK pathway Adult Male Periodontal ligament stem cells Adolescent Cellular differentiation Biophysics Biology Cartilage Oligomeric Matrix Protein Biochemistry p38 Mitogen-Activated Protein Kinases Rats Sprague-Dawley Young Adult Cell Movement Angiopoietin-1 Animals Humans Femur Gene Silencing Progenitor cell Enzyme Inhibitors RNA Small Interfering Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Osteoblasts Tibia Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology musculoskeletal system Molecular biology Receptor TIE-2 Cell biology Protein Structure Tertiary Rats Stem cell Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 455(3-4) |
| ISSN: | 1090-2104 |
| Popis: | Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways. |
| Databáze: | OpenAIRE |
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