Radons, Juergen and Bosserhoff, Anja-Katrin and Grassel, Susanne and Falk, Werner and Schubert, Thomas E. O. (2006) P38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 17 (4). pp. 661-668. ISSN 1107-3756,
Full text not available from this repository. (Request a copy)Abstract
The pleiotropic cytokine interleukin 1 (IL-1) is considered to be the principal inducer of mediators of cartilage degradation in both, osteoarthritis (OA) and rheumatoid arthritis (RA). IL-1 activates numerous signaling pathways involved in cartilage destruction and dedifferentiation of chondrocytes. In this study, we analyzed expression and functional effects of IL-1 in human chondrocytes. We found an IL-1-induced reduction in the expression of the cartilage specific proteoglycan aggrecan as an indicator for the IL-1-mediated dedifferentiation of chondrocytes. To block the IL-1-induced signaling pathways specifically, we incubated human chondrocytes and cartilage explants with IL-1 in the presence of different signal transduction inhibitors and analyzed their effect on aggrecan mRNA expression and IL-6 secretion. IL-6 has been found to act synergistically in the IL-1-induced suppression of the proteoglycan synthesis in chondrocytes. Our results led to the identification of p38MAPK and/or PI3K/JNK as being crucial for IL-1-induced IL-6 secretion by chondrocytes. IL-1-induced down-regulation of aggrecan expression was found to be mediated by p38MAPK and/or ERK1/2. The identification and characterization of these signaling pathways will enable us to develop new modulation strategies for therapeutic use in inflammatory joint diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECEPTOR ACCESSORY PROTEIN; HUMAN ARTICULAR CHONDROCYTES; HUMAN CHONDROSARCOMA CELLS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; RHEUMATOID-ARTHRITIS; OSTEOARTHRITIC CHONDROCYTES; GROWTH-FACTORS; TNF-ALPHA; INTERLEUKIN-1; chondrocytes; IL-1; IL-6; p38MAPK; signal transduction; aggrecan; PI3K; JNK; ERK1/2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Orthopädie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Feb 2021 08:11 |
| Last Modified: | 17 Feb 2021 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34742 |
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