Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc.
Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc.
复制标题
自噬是对椎间盘终板软骨细胞氧化损伤的保护性反应：对退行性腰椎间盘治疗的启示。
DOI：
10.1155/2017/4041768
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发表时间：
2017
影响因子：
--
通讯作者：
Xiao D
中科院分区：
文献类型：
--
作者：
Chen K;Lv X;Li W;Yu F;Lin J;Ma J;Xiao D
下背痛（LBP）是老年人残疾的主要原因。椎间盘退变（IDD）被认为是LBP的主要原因。软骨终板的退变是IDD发生、发展过程中的重要有害因素。氧化应激与IDD有关。然而，软骨终板退变的分子机制仍不清楚。在此，我们发现，氧化应激可以诱导终板软骨细胞凋亡和自噬证明蛋白质印迹分析，流式细胞术，免疫荧光染色，GFP-LC 3B转染，和MDC染色。此外，流式细胞仪检测发现，巴弗洛霉素A1抑制自噬后，终板软骨细胞凋亡明显增加。Western blot结果显示，mTOR通路上游的自噬活性受到明显抑制。结论：氧化应激可促进椎间盘终板软骨细胞的自噬和凋亡。自噬活性的增加可抑制终板软骨细胞的凋亡。氧化应激诱导的终板软骨细胞自噬具有mTOR依赖性。这些发现可能为IDD的发病机制提供新的线索，并为IDD的治疗提供新的策略。
Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD.