TNF/TNFR signal transduction pathway-mediated anti-apoptosis and anti-inflammatory effects of sodium ferulate on IL-1β-induced rat osteoarthritis chondrocytes in vitro

被引:68
作者
Qin, Jun [1 ,2 ]
Shang, Liang [1 ,3 ]
Ping, An-song [2 ]
Li, Jing [1 ]
Li, Xiao-jun [1 ]
Yu, Hong [3 ]
Magdalou, Jacques [4 ]
Chen, Liao-bin [2 ]
Wang, Hui [1 ]
机构
[1] Wuhan Univ, Basic Med Sch, Dept Pharmacol, Wuhan 430071, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Dept Orthopaed Surg, Wuhan 430071, Peoples R China
[3] Wuhan Univ, Basic Med Sch, Dept Biochem, Wuhan 430071, Peoples R China
[4] CNRS UHP, Fac Med, Lab Physiopathol & Pharmacol Articulaires, UMR7561, F-54505 Vandoeuvre Les Nancy, Lorraine, France
基金
中国国家自然科学基金;
关键词
NF-KAPPA-B; HUMAN ARTICULAR CHONDROCYTES; NITRIC-OXIDE SYNTHASE; TRANSCRIPTION FACTORS; TNF-ALPHA; PROTEOGLYCAN SYNTHESIS; INFLAMMATORY RESPONSE; GENE-EXPRESSION; MAP KINASES; CELL-DEATH;
D O I
10.1186/ar4085
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Sodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on the TNF/TNF receptor (TNFR) signal transduction pathway of rat OA chondrocytes. Methods: Primary rat articular chondrocytes were co-treated with IL-1 beta and SF. Chondrocyte apoptosis was assessed by fluorescein isothiocyanate-annexin V/propidium iodide assay. The PCR array was used to screen the expression of 84 key genes involved in apoptosis. The release of TNF alpha and prostaglandin E-2 were analyzed by ELISA. Expressions of proteins were assessed by western blotting. The activity of NF-kappa B was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. The nitric oxide content was measured with the Griess method. Results: After treatment with SF, the apoptosis rate of chondrocytes significantly attenuated (P < 0.01). Results of the apoptosis PCR array suggested that mRNA expression of some core proteins in the TNF/TNFR pathway showed valuable regulation. The protein expressions of TNF alpha, TNFR-1, TNF receptor-associated death domain, caspase-8 and caspase-3 were prevented by SF in a concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with the OA model control (P < 0.01). TNF receptor-associated factor-2 expression, phosphorylations of inhibitor of NF-kappa B kinase (IKK) subunits alpha and beta, and NF-kappa B inhibitor, alpha (I kappa B alpha) were all concentration-dependently suppressed by SF treatment. The results of EMSA showed that SF inhibited the activity of NF-kappa B. In addition, the expressions of cycloxygenase-2 and iNOS and the contents of prostaglandin E-2 and NO were attenuated with the treatment of SF (P < 0.01). Conclusion: SF has anti-apoptosis and anti-inflammatory effects on an OA model induced by IL-1 beta in vitro, which were due to inhibitory actions on the caspase-dependent apoptosis pathway and the IKK/NF-kappa B signal transduction pathway of the TNF/TNFR pathway.
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页数:12
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