Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration

Song, Chao; Xu, Yulin; Peng, Qinghua; Chen, Rui; Zhou, Daqian; Cheng, Kang; Cai, Weiye; Liu, Tao; Huang, Chenyi; Fu, Zhijiang; Wei, Cong; Liu, Zongchao

doi:10.1007/s00011-023-01813-0

Cited by 7 publications

(6 citation statements)

References 67 publications

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“…Through bioinformatic data analysis, we clarified that senescence and apoptosis signaling pathways play an important role in the development of IVDD, and based on our group's previous research and literature, we believe that NPCs are important cells in IVDD. 3 , 14 , 30 , 31 Therefore, we hypothesize that SP1, CASP3, VEGFA, and IL‐6 contribute to the degeneration of NPCs through the regulation of the senescence and apoptosis signaling pathway, which leads to the development of IVDD. First, the effect of LPS on the proliferation of NPCs was investigated.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

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BackgroundIntervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained.AimThis study's objective was to bioinformatics‐based discovery of IVDD biomarkers and immune‐inflammatory infiltrates.Materials and MethodsThe IVDD illness gene collection was gathered from GeneCards, DisGeNet, and gene expression profiles were chosen from the extensive Gene Expression Omnibus database (GSE124272, GSE150408, and GSE153761). The STRING database was used to create a network of protein–protein interactions, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used for functional enrichment analysis. Using hub genes, the immune cell infiltration between IVDD patient samples and control tissues was examined. Finally, quantitative polymerase chain reaction and Western blot experiments were used to verify the expression of hub genes.ResultsA total of 27 differentially expressed hub genes were identified by bioinformatics. According to GO and KEGG analyses, hub genes were prominent in immunological responses, chemokine‐mediated signaling pathways, and inflammatory responses, with the key signaling pathways engaged in cellular senescence, apoptosis, Th1 and Th2 cell differentiation, and Th17 cell differentiation. Immune cell infiltration research revealed that T cells, lymphocytes, B cells, and NK cells were decreased in IVDD patients while monocytes, neutrophils, and CD8 T cells were increased. The expression levels of the senescence hub genes SP1, VEGFA, IL‐6, and the apoptosis key gene CASP3 were considerably greater in the IVDD model group than in the control group, according to in vitro validation.ConclusionIn conclusion, the cellular senescence signaling pathway, the apoptosis signaling pathway, and associated hub genes play significant roles in the development and progression of IVDD, this finding may help direct future research on the senescence signaling route in IVDD.

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Section: Resultsmentioning

confidence: 99%

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

Self Cite

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“…Research into tissue engineering provides new biomaterials, such as alginate hydrogels, to restore or replace IVD tissue. 140 In addition to tissue replacement, further investigations into the cellular mechanisms and pathways involved in the function and dysfunction of IVDs and related structures are providing targeted therapies for restoring IVDs, such as mitochondrial 141 and exosome therapies. 142 These technologies could be valuable tools that increase the repertoire that providers have to treat the root cause of IVD degeneration instead of focusing on palliative care.…”

Section: Emerging Technologies In Ivd Restorationmentioning

confidence: 99%

“…Although largely avascular, mitochondrial-mediated metabolic adaptability plays a role in IVD degeneration. 141 Mitochondria play a role in signalling and regulation, which is key to the function of IVD cells. 154 Biomarkers of IVD degeneration include calcium dysregulation, cytochrome C leakage and increased reactive oxygen species, which are all consequences of mitochondrial dysfunction.…”

Section: Emerging Technologies In Ivd Restorationmentioning

confidence: 99%

Intervertebral disc degeneration and regenerative medicine

Farag,

Rezk,

Hutchinson

et al. 2024

Clinical and Translational Dis

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Intervertebral disc (IVD) degeneration is a common phenomenon that affects patients with increasing prevalence with increasing age. Both conservative treatments, such as the use of pain medication or physical therapy, and surgical treatments, such as fusion or disc replacement therapies, are offered to patients. Both non‐invasive and invasive treatments have been shown to improve pain and quality of life for patients. This review explores the role of regenerative medicine techniques as a promising therapeutic intervention that can be used before or in combination with conservative therapy and surgery to enhance the treatment process in patients with IVD degeneration or disc pathology. Currently, there are four major modules of regenerative medicine: genetic therapy, platelet‐rich plasma therapy, stem cell transplantation and tissue engineering. Several research studies have shown promising outcomes of stem cell transplantation and tissue engineering when combined with either surgical or conservative treatment, resulting in improved pain outcomes. The additional benefit of regenerative medicine techniques, specifically stem cell transplantation, is the potential for treating the root pathology of degeneration. Regenerative medicine techniques also have the potential to either halt or reverse degeneration as opposed to current standards of care for managing symptoms. There is a plethora of current research highlighting the benefits of regenerative medicine techniques; however, there remains clinical concerns and ethical concerns regarding the use of regenerative therapy techniques such as stem cell transplantation in the context of IVD degeneration.

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“…19 Albeit the precise etiology of IVDD remains elusive, augmentation and rehabilitation of mitochondrial function represent a potential avenue for therapeutic intervention. 11,20 Mitochondria are crucial organelles in eukaryotic cells. They serve as the primary energy generators, supplying a large portion of the cell's energy needs.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the development of more effective treatment strategies is urgently needed, and currently available treatment options include biomaterial replacement, drug injection, , gene therapy, , and stem cell therapy . Albeit the precise etiology of IVDD remains elusive, augmentation and rehabilitation of mitochondrial function represent a potential avenue for therapeutic intervention. , …”

Section: Introductionmentioning

confidence: 99%

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction

Chen,

Qian,

et al. 2024

ACS Nano

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As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

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Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration

Cited by 7 publications

References 67 publications

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Intervertebral disc degeneration and regenerative medicine

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction

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