Lactate Down-Regulates Matrix Systhesis and Promotes Apoptosis and Autophagy in Rat Nucleus Pulposus Cells

被引:51
作者
Wu, Wei [1 ]
Zhang, Xiaolei [1 ,2 ]
Hu, Xuqi [1 ]
Wang, Xiangyang [1 ]
Sun, Liaojun [1 ]
Zheng, Xuhao [1 ]
Jiang, Libo [1 ]
Ni, Xiao [1 ]
Xu, Cong [1 ]
Tian, Naifeng [1 ]
Zhu, Siping [1 ]
Xu, Huazi [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Orthopaed, Wenzhou, Peoples R China
[2] Zhejiang Univ, Sch Med, Ctr Stem Cells & Tissue Engn, Hangzhou 310003, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
intervertebral disk degeneration; lactate; apoptosis; autophagy; cell death; INTERVERTEBRAL DISC DEGENERATION; PROTEIN-SYNTHESIS RATES; LOW-BACK-PAIN; SOLUTE TRANSPORT; ANNULUS FIBROSUS; LACTIC-ACID; NUTRITION; OXYGEN; METABOLISM; PROTEOGLYCAN;
D O I
10.1002/jor.22503
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
The intervertebral disk (IVD) is avascular and anaerobic glycolysis has been recognized as the main source of energy. Due to anaerobic glycolysis, there are high levels of lactate production in disk. Previous study shows lactate concentration is elevated in the degenerated IVD. However, it is not clear how lactate causes degeneration of disks. In this study, we found that 2mM lactate promote proliferation of NP cells, while 6mM lactate slightly inhibit their proliferation. By detection under transmission electron microscopy, and western bolt for autophagy related protein beclin-1, LC3 and p62, we demonstrated that 6mM lactate leads to autophagy induction of NP cells. TUNEL results showed that the apoptosis incidence was increased. High lactate concentration induced the degradation in protein expression and mRNA level of GAG content, type II collagen and slight increase of type I collagen. Based on these observations, we conclude that high lactate concentration is a pathogenic factor for IVD degeneration, and lactate metabolism may be a new therapeutic target for IVD degeneration. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:253-261, 2014.
引用
收藏
页码:253 / 261
页数:9
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