The interplay between JNK pathway activation, proteoglycan turnover and endocytosis in chondrocytes
Ismail HM., Yamamoto K., Nagase H., Vincent TL., Troeberg L., Saklatvala J.
The JNK pathway (c-jun N-terminal kinase) is activated by a variety of inflammatory and physical stressful stimuli. Recently, we identified a new and an important role for the JNK pathway in the turnover of the cartilage proteoglycan aggrecan. Loss of JNK2 isoform in human chondrocytes and murine cartilage abolished IL1- induced aggrecan degradation and aggrecanase activity. Furthermore, JNK2-null mice were protected from surgically-induced osteoarthritis. Here we show that the JNK2-dependent effect on the aggrecan degradation is linked to an LRP1-dependent endocytic mechanism.