Life Sciences, Journal Year: 2019, Volume and Issue: 228, P. 85 - 97
Published: April 30, 2019
Language: Английский
Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2082 - 2092
Published: Sept. 24, 2020
Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis function important. Mitophagy, a process that selectively clears damaged or dysfunctional through autophagic machinery, functions to maintain mitochondrial quality control homeostasis. IVDD OA are similar joint diseases involving degradation cartilaginous tissues mainly caused by oxidative stress, cell apoptosis extracellular matrix (ECM) degradation. Over past decade, accumulating evidence indicates essential role mitophagy pathogenesis OA. Importantly, strategies regulation exert beneficial effects pre-clinical experiments. Given importance novelty mitophagy, we provide an overview pathways discuss roles We also highlight potential targeting for treatment diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B 3-like; CDH6: cadherin 6; CEP: endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin beta; IMM: inner membranes; IVDD: degeneration; MAPK8/JNK: mitogen-activated kinase 8; MFN1: mitofusin MFN2: 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: transmembrane potential; CALCOCO2/NDP52: calcium binding coiled-coil domain NFE2L2: nuclear factor: erythroid 2 like NP: nucleus pulposus; OA: osteoarthritis; OPA1: GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin ligase; PD: Parkinson PGAM5: PGAM 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator alpha; PHF23: PHD finger 23; PINK1: PTEN induced putative ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin SIRT2: SIRT3: SQSTM1/p62: sequestosome TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.
Language: Английский
Citations
297
Free Radical Biology and Medicine, Journal Year: 2019, Volume and Issue: 143, P. 1 - 15
Published: July 24, 2019
Language: Английский
Citations
239
Cell Proliferation, Journal Year: 2020, Volume and Issue: 53(3)
Published: Feb. 5, 2020
Mitochondrial dysfunction, oxidative stress and nucleus pulposus (NP) cell apoptosis are important contributors to the development pathogenesis of intervertebral disc degeneration (IDD). Here, we comprehensively evaluated effects mitochondrial dynamics, mitophagic flux Nrf2 signalling on quality control, ROS production NP survival in vitro ex vivo compression models IDD explored mitochondria-targeted anti-oxidant MitoQ its mechanism.Human cells were exposed mechanical mimic pathological conditions.Compression promoted stress, dysfunction apoptosis. Mechanistically, disrupted fission/fusion balance, inducing fatal fission. Concomitantly, PINK1/Parkin-mediated mitophagy was activated, whereas blocked. pathway insufficiently activated. These caused damaged mitochondria accumulation persistent damage. Moreover, restored dynamics alleviated impairment mitophagosome-lysosome fusion lysosomal function enhanced activity. Consequently, eliminated, redox balance improved, increased. Additionally, an rat model.These findings suggest that comodulation alleviates sustained represents a promising therapeutic strategy for IDD; furthermore, our results provide evidence might serve as effective agent this disorder.
Language: Английский
Citations
144
Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)
Published: Jan. 1, 2021
Ferroptosis is a specialized form of regulated cell death that charactered by iron‐dependent lethal lipid peroxidation, process associated with multiple diseases. However, its role in the pathogenesis intervertebral disc degeneration (IVDD) rarely investigated. This study aimed at investigating ferroptosis oxidative stress‐ (OS‐) induced nucleus pulposus (NPC) decline and IVDD determine underlying regulatory mechanisms. We used tert‐butyl hydroperoxide (TBHP) to simulate OS conditions around human NPCs. Flow cytometry transmission electron microscopy were identify ferroptosis, while iron assay kit, Perl’s staining, western blotting performed intracellular levels. A ferroportin‐ (FPN‐) lentivirus FPN‐siRNA constructed explore relationship between FPN, homeostasis, ferroptosis. Furthermore, hinokitiol, bioactive compound known specifically resist restore FPN function, was evaluated for therapeutic both vitro vivo . The results indicated intercellular overload plays an essential TBHP‐induced Mechanistically, dysregulation responsible under OS. increase nuclear translocation metal‐regulatory transcription factor 1 (MTF1) restored function abolished overload, protected cells against Additionally, hinokitiol enhanced MTF1 suppressing JNK pathway ameliorated progression Taken together, our demonstrate dysfunction are involved NPC depletion To best knowledge, this first protective NPCs, suggesting potential as novel target IVDD.
Language: Английский
Citations
104
Biomaterials, Journal Year: 2021, Volume and Issue: 274, P. 120850 - 120850
Published: May 6, 2021
Language: Английский
Citations
104
Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(8), P. 1067 - 1075
Published: Aug. 17, 2022
Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and recognized as major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, therapeutic strategies for are currently limited. Oxidative stress plays pivotal roles in pathogenesis progression of many age-related diseases humans, including IDD. Nuclear factor E2-related 2 (Nrf2) master antioxidant transcription that protects cells against oxidative damage. Nrf2 negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) exerts important effects on progression. Accumulating evidence has revealed can facilitate downstream genes binding response elements (AREs) promoter regions, heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), NADPH quinone dehydrogenase (NQO1). The defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, inflammatory nucleus pulposus (NP), calcification cartilaginous endplates (EP) In this review, we aim discuss current knowledge systematically.
Language: Английский
Citations
98
Nature Reviews Rheumatology, Journal Year: 2023, Volume and Issue: 19(3), P. 136 - 152
Published: Jan. 26, 2023
Language: Английский
Citations
93
Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16
Published: Jan. 12, 2022
Intervertebral disc degeneration is a very common type of degenerative disease causing severe socioeconomic impact, as well major cause discogenic low back pain and herniated discs, placing heavy burden on patients the clinicians who treat them. IDD known to be associating with complex process involving in extracellular matrix cellular damage, recent years, there increasing evidence that oxidative stress an important activation mechanism reactive oxygen nitrogen species regulate metabolism, proinflammatory phenotype, autophagy senescence intervertebral cells, apoptosis, autophagy, senescence. Despite tremendous efforts researchers within field pathogenesis, proven strategies prevent this are still limited. Up now, several antioxidants have been proved effective for alleviating IDD. In article, we discussed accelerates by influencing aging, inflammation, DNA methylation, summarize some antioxidant therapeutic measures IDD, indicating therapy holds excellent promise.
Language: Английский
Citations
87
Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(9)
Published: March 13, 2023
Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.
Language: Английский
Citations
85
Advanced Science, Journal Year: 2023, Volume and Issue: 10(13)
Published: March 23, 2023
Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe
Language: Английский
Citations
82