期刊
RHEUMATOLOGY
卷 53, 期 6, 页码 1022-1033出版社
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/ket471
关键词
meniscus; autophagy; apoptosis; JNK
类别
资金
- National Natural Science Foundation of China [81101379, 81171705, 81000793]
- Natural Science Fund of the Shanghai Jiao Tong University School of Medicine [11XJ21022]
Objective. Autophagy is a potential protective mechanism that is involved in several degenerative diseases. Nitric oxide (NO) is associated with programmed cellular death in meniscal cells, but whether it can induce autophagy is still undetermined. This study aims to investigate the interaction between autophagy and NO in normal human meniscal cells. Methods. Normal meniscal cells were harvested from female patients. NO donors and NO synthase inhibitors were used to regulate the level of NO. Changes in the incidence of autophagy and apoptosis were examined using flow cytometry, western blot and immunofluorescence methods. The effects of NO-mediated autophagy regulation of the expression of MMPs and aggrecanases (ADAMTS-4 and -5) were analysed by real-time PCR. Results. NO donors inhibited autophagy as well as augmented apoptosis in human meniscal cells with serum deprivation. Conversely, treatment with NOS inhibitors resulted in up-regulation of the autophagy level while repressing apoptosis. NOS inhibitor treatment also resulted in down-regulation of MMPs and aggrecanase mRNA expression. This effect of NOS inhibitor was also blocked by autophagy inhibitors. Our results also showed that NOS inhibitor enhanced Jun-N-terminal kinase (JNK) activation. Furthermore, SP600125, a selective JNK inhibitor, blocked up-regulation of autophagy by NOS inhibitor. Conclusion. Our results demonstrated that NO augmented serum deprivation-induced apoptosis of meniscal cells via inhibition of autophagy through inactivation of JNK. Up-regulation of autophagy may be a potential approach in the treatment of meniscal tissue degeneration.
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