459 MODULATION OF IN VITRO WEAR OF ARTICULATING CARTILAGE: EFFECT OF SYNOVIAL FLUID AND CARTILAGE DEGENERATION
| Autor: | H.H. Harith, Michele M. Temple-Wong, Van W. Wong, K.M. Keifer, Martin Lotz, William D. Bugbee, Q.T. Nguyen, Robert L. Sah |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
030203 arthritis & rheumatology
MAPK/ERK pathway 0303 health sciences Chemistry Cartilage Biomedical Engineering GTPase Chondrocyte nervous system diseases Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation Rheumatology medicine Phosphorylation LY294002 Orthopedics and Sports Medicine Aggrecan 030304 developmental biology |
| Zdroj: | Osteoarthritis and Cartilage. 16 |
| ISSN: | 1063-4584 |
| DOI: | 10.1016/s1063-4584(08)60500-2 |
| Popis: | CTS-induced RAS activation resulted in c-Raf phosphorylation. However, c-Raf activation was not mediated via PAK phosphorylation and was not inhibited by LY294002. These results suggested that RAS activated c-Raf directly without PI-3-kinase mediated PAK-1 activation. CTS induced c-RAF activation was followed by MEK1/2 (Ser217/221) phosphorylation, which in turn phosphorylated ERK 1/2. Interestingly, Il-1b induced ERK activation was mediated by RAS GTPase activity, however, its activation cascade was distinct from CTS induced ERK1/2 activation. Examination of down stream events revealed that in parallel to ERK activation, CTS induced an increase in c-Myc phosphorylation and upregulation of c-myc, VEGF, ERK 1/2, aggrecan, gene transcription. Furthermore, inhibition of MEK1 by PD98059 inhibited CTS-induced upregulation of c-myc and VEGF mRNA expression. Conclusions: The results demonstrate that the anabolic actions of mechanical signals, at least in part, are mediated via ERK signaling cascade. Furthermore, CTS upregulated RAS GTPase activity to initiate ERK signaling cascade that results in the induction of genes such as VEGF and c-myc that are associated with chondrocyte growth and proliferation. Acknowledgement. NIH AT00646, AR04878, NIDCR DE15399. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect