Open AccessCompression‐induced senescence of nucleus pulposus cells by promoting mitophagy activation via the PINK1/PARKIN pathway
Author(s) -
Huang Donghua,
Peng Yizhong,
Li Zhiliang,
Chen Sheng,
Deng Xiangyu,
Shao Zengwu,
Ma Kaige
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15256
Subject(s) - mitophagy , parkin , pink1 , microbiology and biotechnology , mitochondrion , senescence , small hairpin rna , biology , chemistry , autophagy , gene knockdown , biochemistry , parkinson's disease , medicine , pathology , apoptosis , disease
The current research aimed to explore the possible relationship between PINK1/PARKIN‐mediated mitophagy and the compression‐induced senescence of nucleus pulposus cells (NPCs). Therefore, the stages of senescence in NPCs were measured under compression lasting 0, 24 and 48 hours. The mitophagy‐related markers, autophagosomes and mitochondrial membrane potential were tested to determine the levels of PINK1/PARKIN‐mediated mitophagy under compression. The PINK1 and PARKIN levels were also measured by immunohistochemistry of human and rat intervertebral disc (IVD) tissues taken at different degenerative stages. A specific mitophagy inhibitor, cyclosporine A (CSA) and a constructed PINK1‐shRNA were used to explore the relationship between mitophagy and senescence by down‐regulating the PINK1/PARKIN‐mediated mitophagy levels. Our results indicated that compression significantly enhanced the senescence of NPCs in a time‐dependent manner. Also, PINK1/PARKIN‐mediated mitophagy was found to be activated by the extended duration of compression on NPCs as well as the increased degenerative stages of IVD tissues. After inhibition of PINK1/PARKIN‐mediated mitophagy by CSA and PINK1‐shRNA, the senescence of NPCs induced by compression was strongly rescued. Hence, the excessive degradation of mitochondria in NPCs by mitophagy under continuous compression may accelerate the senescence of NPCs. Regulating PINK1/PARKIN‐mediated mitophagy might be a potential therapeutic treatment for IVD degeneration.