Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment

被引:30
作者
Xie, Jingjing [1 ]
Li, Bo [1 ]
Yao, Bing [1 ]
Zhang, Pingchao [1 ]
Wang, Lixin [1 ]
Lu, Hua [1 ]
Song, Xuan [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Chongming Branch, Xinhua Hosp,Dept Orthoped Surg, Shanghai 202150, Peoples R China
关键词
HUMAN INTERVERTEBRAL DISC; ALPHA-INDUCED APOPTOSIS; FAS LIGAND; TNF-ALPHA; EXPRESSION; BETA; DEGENERATION; PROTECTS; DEATH; SMAD3;
D O I
10.1042/BSR20191726
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-alpha is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-beta 1 has the potential to regenerate degenerative disc. Objective: To investigate the protective role of TGF-beta 1 against TNF-alpha-mediated NP cell apoptosis and the underlying mechanism. Methods: Rat NP cells were treated with TNF-alpha (100 ng/ml) for 48 h. TGF-beta 1 was added into the culture medium to investigate its protective effects against TNF-alpha-induced NP cell apoptosis. Exogenous FasL was used to investigate the potential role of the Fas/FasL pathway in this process. Flow cytometry assay was used to analyze NP cell apoptosis. Real-time PCR and Western blotting were used to analyze gene and protein expression of apoptosis-related molecules. Results: In TNF-alpha-treated NP cells, TGF-beta 1 significantly decreased NP cell apoptosis, declined caspase-3 and -8 activity, and decreased expression of Bax and caspase-3 (cleaved-caspase-3) but increased expression of Bcl-2. However, exogenous FasL partly reversed these effects of TGF-beta 1 in NP cells treated with TNF-alpha. Additionally, expression of Fas and FasL in TNF-alpha-treated NP cells partly decreased by TGF-beta 1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-beta 1 and TNF-alpha. Conclusion: TGF-beta 1 helps to inhibit TNF-alpha-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-beta 1 may be effective to retard inflammation-mediated disc degeneration.
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页数:8
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