The Role of IL-17-Mediated Inflammatory Processes in the Pathogenesis of Intervertebral Disc Degeneration and Herniation: A Comprehensive Review

Suyama, Kaori; Sakai, Daisuke; Watanabe, Masahiko

doi:10.3389/fcell.2022.857164

Cited by 15 publications

(9 citation statements)

References 87 publications

(155 reference statements)

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“…The enriched KEGG pathways included the following: IL-17 signaling pathway, PI3K/Akt signaling pathway, JAK/STAT signaling pathway, FoxO signaling pathway, AGE/RAGE signaling pathway, and AMPK signaling pathway. During IDD progression, cytokines trigger Th17 cells to increase IL-17 production locally in IVD [ 37 , 38 ]. The JAK/STAT and PI3K/AKT pathways are important signaling pathways for IL-17-mediated IDD.…”

Section: Discussionmentioning

confidence: 99%

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

付洛安

2023

BMC Musculoskelet Disord

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Intervertebral disc degeneration (IDD) is considered one of the main causes of low back pain and lumbar disc herniation. Various studies have shown that disc cell senescence plays a critical role in this process. however, its role in IDD is yet unclear. In this study, we explored the role of senescence-related genes (SR-DEGs) and its underlying mechanism in IDD. A total of 1325 differentially expressed genes (DEGs) were identified using Gene Expression Omnibus (GEO) database GSE41883. 30 SR-DEGs were identified for further functional enrichment and pathway analysis, and two hub SR-DEGs (ERBB2 and PTGS2) were selected to construct transcription factor (TF)–gene interaction and TF-miRNA coregulatory networks, and 10 candidate drugs were screened for the treatment of IDD. Last but not least, in vitro experiments show that ERBB2 expression decreased and PTGS2 expression increased in human nucleus pulposus (NP) cell senescence model treated with TNF-α. After lentivirus-mediated overexpression of ERBB2, the expression of PTGS2 decreased and the senescence level of NP cells decreased. Overexpression of PTGS2 reversed the anti-senescence effects of ERBB2. The findings in this study suggested that ERBB2 overexpression further reduced NP cell senescence by inhibiting PTGS2 levels, which ultimately alleviated IDD. Taken together, our findings provide new insights into the roles of senescence-related genes in IDD and highlight a novel target of ERBB2-PTGS2 axis for therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

付洛安

2023

BMC Musculoskelet Disord

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“…It has been argued that the excessive apoptosis of NPCs is a classical pathological change in IDD ( 31 ). Additionally, previous studies have illuminated that inflammation may be a risk factor for NPC apoptosis and is involved in the process of IDD ( 32 , 33 ). Additionally, ER stress has been determined to be responsible for normal cell metabolism and to provoke the apoptosis of NPCs ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Panax notoginseng saponin reduces IL-1β-stimulated apoptosis and endoplasmic reticulum stress of nucleus pulposus cells by suppressing miR-222-3p

et al. 2022

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Background It is well documented that the malignant biological behaviors of nucleus pulposus cells (NPCs) could trigger intervertebral disc degeneration (IDD). Panax notoginseng saponin (PNS) is a traditional Chinese medicine that inhibits osteoclastogenesis. However, its effects on the phenotypes of NPCs in IDD remains largely unknown. This study sought to examine the role of PNS in IDD and its regulatory mechanism. Methods First, human NPCs (hNPCs) were treated with interleukin-1 beta ( IL-1β ) to induce an IDD cell model. Cell proliferation and apoptosis were estimated by Cell Counting Kit-8 (CCK-8) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Western blot was employed to examine the levels of proteins related to apoptosis and endoplasmic reticulum (ER) stress. Enzyme-linked immunosorbent assays (ELISAs) were used to test inflammatory factors levels. Immunofluorescence (IF) assays were used to determine the nuclear translocation of nuclear factor-kappa beta ( NF-κB ) p65 . Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-222-3p expression. Results We discovered that PNS enhanced the viability but reduced the apoptosis, inflammation, and ER stress response of IL-1β -induced hNPCs in a concentration-dependent manner. Additionally, PNS significantly reduced miR-222-3p expression in the IL-1β -induced hNPCs. Notably, these PNS effects were reversed by the upregulation of miR-222-3p . Conclusions In summary, PNS appears to facilitate the proliferation and attenuate the apoptosis, inflammatory response, and ER stress response of IL-1β -induced hNPCs by inhibiting miR-222-3p expression. Our findings provide a theoretical basis for a novel drug application in IDD research.

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“…Therefore, IL-17 levels may be associated with the extent of IVDD ( 112 ). IVDD exposure to TNF-α stimulates the production of IL-17, which promotes the degradation of the ECM mainly through the IL-17A receptor-nuclear factor kappa B (NF-κB) pathway ( 114 ). IL-17A receptors are mainly distributed on the surfaces of NP cells; therefore, the inhibition of IL-17A receptors can attenuate ECM degradation and delay IVDD.…”

Section: Regulation Of the Inflammatory Microenvironmentmentioning

confidence: 99%

Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment

et al. 2023

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Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo. It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development.

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The Role of IL-17-Mediated Inflammatory Processes in the Pathogenesis of Intervertebral Disc Degeneration and Herniation: A Comprehensive Review

Cited by 15 publications

References 87 publications

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

Panax notoginseng saponin reduces IL-1β-stimulated apoptosis and endoplasmic reticulum stress of nucleus pulposus cells by suppressing miR-222-3p

Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment

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