Regulation of Gene Expression by PI3K in Mouse Growth Plate Chondrocytes
| Autor: | Claudine G. James, Frank Beier, Veronica Ulici, Katie D. Hoenselaar |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cellular differentiation
Medical Physiology lcsh:Medicine Chondrocyte hypertrophy Cell Biology/Cell Signaling Rheumatology/Cartilage Biology and Osteoarthritis Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Developmental Growth Plate lcsh:Science Cells Cultured Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Multidisciplinary Blotting Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Cell Differentiation Genetics and Genomics/Gene Expression Endochondral bone growth Up-Regulation Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Western Signal Transduction Research Article Morpholines Blotting Western Down-Regulation Biology Chondrocyte Cell and Developmental Biology 03 medical and health sciences Chondrocytes medicine Animals Endochondral ossification Cell Biology/Gene Expression PI3K/AKT/mTOR pathway 030304 developmental biology Cartilage lcsh:R Genetics and Genomics Cultured Cells Molecular biology Gene Expression Regulation Chromones lcsh:Q |
| Zdroj: | PLoS ONE Physiology and Pharmacology Publications PLoS ONE, Vol 5, Iss 1, p e8866 (2010) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0008866 |
| Popis: | Background Endochondral ossification, the process through which long bones are formed, involves chondrocyte proliferation and hypertrophic differentiation in the cartilage growth plate. In a previous publication we showed that pharmacological inhibition of the PI3K signaling pathway results in reduced endochondral bone growth, and in particular, shortening of the hypertrophic zone in a tibia organ culture system. In this current study we aimed to investigate targets of the PI3K signaling pathway in hypertrophic chondrocytes. Methodology/Principal Findings Through the intersection of two different microarray analyses methods (classical single gene analysis and GSEA) and two different chondrocyte differentiation systems (primary chondrocytes treated with a pharmacological inhibitor of PI3K and microdissected growth plates), we were able to identify a high number of genes grouped in GSEA functional categories regulated by the PI3K signaling pathway. Genes such as Phlda2 and F13a1 were down-regulated upon PI3K inhibition and showed increased expression in the hypertrophic zone compared to the proliferative/resting zone of the growth plate. In contrast, other genes including Nr4a1 and Adamts5 were up-regulated upon PI3K inhibition and showed reduced expression in the hypertrophic zone. Regulation of these genes by PI3K signaling was confirmed by quantitative RT-PCR. We focused on F13a1 as an interesting target because of its known role in chondrocyte hypertrophy and osteoarthritis. Mouse E15.5 tibiae cultured with LY294002 (PI3K inhibitor) for 6 days showed decreased expression of factor XIIIa in the hypertrophic zone compared to control cultures. Conclusions/Significance Discovering targets of signaling pathways in hypertrophic chondrocytes could lead to targeted therapy in osteoarthritis and a better understanding of the cartilage environment for tissue engineering. |
| Databáze: | OpenAIRE |
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