Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc.
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.
Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, China.
Ke
0000-0003-2641-8483
K
Chen
Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong 524023, China.
Xiaohua
0000-0002-7514-2631
X
Lv
Department of Orthopaedics, Peking University Shenzhen Hospital, Guangdong 518036, China.
Wei
0000-0003-2898-3988
W
Li
Department of Orthopaedics, Peking University Shenzhen Hospital, Guangdong 518036, China.
Fei
F
Yu
Department of Orthopaedics, Peking University Shenzhen Hospital, Guangdong 518036, China.
Jianjing
0000-0002-1586-1415
J
Lin
Department of Orthopaedics, Peking University Shenzhen Hospital, Guangdong 518036, China.
Junxuan
J
Ma
Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 518036, China.
Deming
0000-0003-0913-3654
D
Xiao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D007403:Intervertebral Disc / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology*; D018942:Macrolides / Q000633:toxicity; D008297:Male; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009045:Motor Endplate / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D006861:Hydrogen Peroxide; D018942:Macrolides; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D051028:bcl-2-Associated X Protein; C526109:Anxa3 protein, rat; C040929:bafilomycin A1