IL‐17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications

Tan, Jing‐Hua; Li, Ze‐Peng; Liu, Lu‐Lu; Líu, Hao; Xue, Jing

doi:10.1002/cbin.11767

Cited by 19 publications

(17 citation statements)

References 150 publications

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“…Using the Venn diagram, there were 42 co-DEGs in annulus cells induced by TNF-α and IL-1β, which were mainly enriched in the response to LPS and molecules of bacterial origin and the regulation of receptor ligand activity and signaling receptor activator activity according to GO analysis. In addition, the following signaling pathways enriched through KEGG analysis, mainly including TNF signaling pathway [33], IL-17 signaling pathway [34], NF-κB signaling pathway [35], and NOD-like receptor signaling pathway [36], play crucial roles in the activity of catabolic genes and inflammatory mediators during the pathological process of IVDD as demonstrated by previous researche. Furthermore, a PPI network based on co-DEGs was constructed to obtain the hub genes (CXCL1, CXCL2, CXCL8, IL1β, and PTGS2).…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1β Induced Inflammatory Response in Intervertebral Disc Degeneration

Chen

Han

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. The determination of miRNA-mRNA pairs for intervertebral disc degeneration (IVDD) regulated by pro-inflammatory cytokines were investigated. Methods. Two dataset (accession number GSE27494 and GSE41883 from platform GPL1352) of expression profiling was downloaded from Gene Expression Omnibus (GEO). The annulus cells were isolated from annulus fibrosus in patients with degenerative disc disease. The cells were then cultured in a three-dimensional (3D) collagen containing with/without proinflammatory cytokines (tumor necrosis factor alpha (TNF-α) or interleukin beta (IL-1β)). After being cultured for 14 days, the isolated total RNA was analyzed via microarray, and the expression array data were obtained using BRB-Array Tools followed by analyzing the differentially expressed genes (DEGs) and the prediction of potential miRNA targets of hub genes through online database. Results. Firstly, 52 and 296 DEGs were found in IL-1β- and TNF-α-induced annulus cells, respectively, of these there had 42 common DEGs (co-DEGs) with 34 increased transcripts and 8 reduced ones. Based on the GO and KEGG software, these co-DEGs were mainly enriched in the response to lipopolysaccharide (LPS) and molecule of bacterial origin, the regulation of receptor ligand activity and signaling receptor activator activity, as well as the following signaling pathways, including TNF signaling pathway, IL-17 signaling pathway, and NF-κB signaling pathway. Top hub genes (CXCL1, CXCL2, CXCL8, IL1Β and PTGS2) regulated by several potential microRNAs were involved in TNF-α/IL-1β treated annulus cells. Conclusions. Several candidate genes regulated by miRNAs caused by TNF-α/IL-1β in the annulus cells were found, which will guide diagnosis and treatment for degenerative disc disease.

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Section: Discussionmentioning

confidence: 99%

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1β Induced Inflammatory Response in Intervertebral Disc Degeneration

Chen

Han

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…The most enriched biological process was Response to oxidative stress, cellular component was Cytoplasm, and molecular function was Identical protein binding. More importantly, we also investigated the potential signaling pathways involved in the repair process of NPCs cocultured with MSCs, and some of these signaling pathways have been proved to play important roles in the pathophysiology of IDD [38][39][40][41][42]. TNF signaling pathway and IL-17 signaling pathway both were inflammation-related pathways, which indicated that MSCs might reduce the oxidative stress, and then improve the inflammatory status of degenerative NPCs [38,39].…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, we also investigated the potential signaling pathways involved in the repair process of NPCs cocultured with MSCs, and some of these signaling pathways have been proved to play important roles in the pathophysiology of IDD [38][39][40][41][42]. TNF signaling pathway and IL-17 signaling pathway both were inflammation-related pathways, which indicated that MSCs might reduce the oxidative stress, and then improve the inflammatory status of degenerative NPCs [38,39]. MAPK signaling pathway was another vital biolog-ical pathway in the development of IDD [40][41][42] 7 Stem Cells International degenerative NPCs cocultured with MSCs.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

Zhao

Xiang

Cheng

et al. 2022

Stem Cells International

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Background. Stem cell therapy is a promising therapeutic modality for intervertebral disc degeneration (IDD). Oxidative stress is a vital contributor to the IDD; however, the definite role of oxidative stress in stem cell therapy for IDD remains obscure. The aim of this study was to determine the vital role of oxidative stress-related differentially expressed genes (OSRDEGs) in degenerative NPCs cocultured with mesenchymal stem cells (MSCs). Methods. A series of bioinformatic methods were used to calculate the oxidative stress score and autophagy score, identify the OSRDEGs, conduct the function enrichment analysis and protein-protein interaction (PPI) analysis, build the relevant competing endogenous RNA (ceRNA) regulatory networks, and explore the potential association between oxidative stress and autophagy in degenerative NPCs cocultured with MSCs. Results. There was a significantly different oxidative stress score between NPC/MSC samples and NPC samples ( p < 0.05 ). Forty-one OSRDEGs were selected for the function enrichment and PPI analyses. Ten hub OSRDEGs were obtained according to the PPI score, including JUN, CAT, PTGS2, TLR4, FOS, APOE, EDN1, TXNRD1, LRRK2, and KLF2. The ceRNA regulatory network, which contained 17 DElncRNAs, 240 miRNAs, and 10 hub OSRDEGs, was constructed. Moreover, a significant relationship between the oxidative stress score and autophagy score was observed ( p < 0.05 ), and 125 significantly related gene pairs were obtained ( r > 0.90 , p < 0.05 ). Conclusion. Stem cell therapy might repair the degenerative IVD via reducing the oxidative stress through the ceRNA regulatory work and restoration of autophagy in degenerative NPCs. This research could provide new insights into the mechanism research of stem cell therapy for IDD and potential therapeutic targets in the IDD treatment.

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“…IFN-γ was reported to affect tissue-specific macrophages in NP. Furthermore, several angiogenic and neurogenic factors have also been linked to the degeneration of IVDs, conducting to blood vessels and nerve in-growth [ 12 , 20 , 25 , 26 , 27 , 28 ].…”

Section: Pathogenesis and Etiology Of Intervertebral Disc Degenerationmentioning

confidence: 99%

Recent Advances in Managing Spinal Intervertebral Discs Degeneration

Costăchescu

Niculescu

Teleanu

et al. 2022

IJMS

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Low back pain (LBP) represents a frequent and debilitating condition affecting a large part of the global population and posing a worldwide health and economic burden. The major cause of LBP is intervertebral disc degeneration (IDD), a complex disease that can further aggravate and give rise to severe spine problems. As most of the current treatments for IDD either only alleviate the associated symptoms or expose patients to the risk of intraoperative and postoperative complications, there is a pressing need to develop better therapeutic strategies. In this respect, the present paper first describes the pathogenesis and etiology of IDD to set the framework for what has to be combated to restore the normal state of intervertebral discs (IVDs), then further elaborates on the recent advances in managing IDD. Specifically, there are reviewed bioactive compounds and growth factors that have shown promising potential against underlying factors of IDD, cell-based therapies for IVD regeneration, biomimetic artificial IVDs, and several other emerging IDD therapeutic options (e.g., exosomes, RNA approaches, and artificial intelligence).

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IL‐17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications

Cited by 19 publications

References 150 publications

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1β Induced Inflammatory Response in Intervertebral Disc Degeneration

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1β Induced Inflammatory Response in Intervertebral Disc Degeneration

Mesenchymal Stem Cells May Alleviate the Intervertebral Disc Degeneration by Reducing the Oxidative Stress in Nucleus Pulposus Cells

Recent Advances in Managing Spinal Intervertebral Discs Degeneration

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