c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis.

Publisher: Canadian Science Publishing Country of Publication: Canada NLM ID: 0372712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1205-7541 (Electronic) Linking ISSN: 00084212 NLM ISO Abbreviation: Can J Physiol Pharmacol Subsets: MEDLINE

Publication: 2011- : Ottawa, ON : Canadian Science Publishing
Original Publication: Ottawa, National Research Council of Canada.

Apoptosis Regulatory Proteins/*metabolism ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Membrane Proteins/*metabolism ; Osteoarthritis/*metabolism ; Proto-Oncogene Proteins/*metabolism; Aged ; Animals ; Anthracenes/pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins/genetics ; Bcl-2-Like Protein 11 ; Chondrocytes/drug effects ; Chondrocytes/metabolism ; Chondrocytes/pathology ; Humans ; Interleukin-1beta/metabolism ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors ; MAP Kinase Signaling System ; Membrane Proteins/genetics ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Osteoarthritis/pathology ; Proto-Oncogene Proteins/genetics ; Transcriptional Activation

Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1β has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) - c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1β. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1β, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK-c-Jun pathway was observed under IL-1β treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK-c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1β. These findings suggest that the JNK-c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK-c-Jun-Bim pathway is vital for chondrocyte apoptosis.

0 (Anthracenes)
0 (Apoptosis Regulatory Proteins)
0 (BCL2L11 protein, human)
0 (Bcl-2-Like Protein 11)
0 (Bcl2l11 protein, mouse)
0 (Interleukin-1beta)
0 (Membrane Proteins)
0 (Proto-Oncogene Proteins)
1TW30Y2766 (pyrazolanthrone)
EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)

Date Created: 20140208 Date Completed: 20140815 Latest Revision: 20161125

20231215

10.1139/cjpp-2013-0228

24502636