title: c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis.
abstract: 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.
authors: a Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Zhiqiang
authors: Z
authors: Ye
authors: Yuxian
authors: Y
authors: Chen
authors: Rongkai
authors: R
authors: Zhang
authors: Haitao
authors: H
authors: Dai
authors: Chun
authors: C
authors: Zeng
authors: Hua
authors: H
authors: Zeng
authors: Hui
authors: H
authors: Feng
authors: Gengheng
authors: G
authors: Du
authors: Hang
authors: H
authors: Fang
authors: Daozhang
authors: D
authors: Cai
mesh_terms: D000368:Aged; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000873:Anthracenes; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D053583:Interleukin-1beta; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases