Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression

Zhen-qiang, LI; Sun, Congjian; Chen, Maosong; Wang, Boding

doi:10.1080/21655979.2021.1973781

Cited by 10 publications

(6 citation statements)

References 37 publications

(50 reference statements)

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“…[ 56 ] Studies have revealed a connection between inflammation and metabolic alterations in nucleus pulposus cells, which is in turn associated with LDH. [ 57 ] In the context of low back pain, there is a strong correlation between LDH and inflammation. [ 58 ] As mentioned earlier, there is a reduction in the survival of dorsal root ganglion neurons in cases of LDH, accompanied by an increase in both apoptosis and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis

Chen,

Yu,

et al. 2024

Medicine

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Previous observational studies have observed a correlation between sedentary behavior and osteoporosis. However, conclusions from these studies have been contradictory. To explore the potential causal relationship between sedentary behavior and osteoporosis, we conducted a Mendelian randomization analysis. A two-sample Mendelian randomization was adopted to explore the causal relationship of leisure sedentary behavior with osteoporosis. We employed 5 methods to estimate the causal associations between leisure sedentary behavior and osteoporosis. Univariable Mendelian randomization results provided evidence for the causal relationship of the time spent on computer-use with the bone mineral density estimated by heel quantitative ultrasound (eBMD) (inverse variance weighted [IVW]: β (95% confidence interval [CI]) − 0.150 (−0.270 to −0.031), P = .013; weighted median: β (95%CI) − 0.195 (−0.336 to −0.055), P = .006). Similar associations were observed in the driving forearm bone mineral density (FABMD) (IVW: β (95%CI) − 0.933 (−1.860 to −0.007), P = .048) and driving lumbar spine bone mineral density (IVW: β (95%CI) − 0.649 (−1.175 to −0.124), P = .015). However, we did not find a significant causal relationship between the time spent on watching TV and bone mineral density. Research showed that there was a causal relationship between the time spent on computer use and driving time and eBMD, FABMD, and lumbar spine bone mineral density.

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Section: Discussionmentioning

confidence: 99%

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis

Chen,

Yu,

et al. 2024

Medicine

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“…Our study found that p-p38 was highly expressed in ex vivo IVD, but collagen II was decreased. Additionally, several studies have suggested that targeting p38MAPK may be able to treat IDD [ 42 , 43 ]. The overall effect mechanism of TAK-715 in NPCs was described in Fig.…”

Section: Discussionmentioning

confidence: 99%

TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo

Wang

Yao

et al. 2023

Arthritis Res Ther

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Background Intervertebral disc degeneration (IDD) is one of the most common disorders related to the spine. Inflammation, apoptosis and extracellular matrix (ECM) degradation contribute to disc degeneration in nucleus pulposus cells (NPCs). This study focused on the role and mechanism of the p38 inhibitor TAK-715 in intervertebral disc degeneration. Methods NPCs were treated with IL-1β to mimic apoptosis, followed by the addition of TAK-715. It was determined that apoptosis, inflammatory mediators (COX-2), inflammatory cytokines (HMGB1), and ECM components (collagen II, MMP9, ADAMTS5, and MMP3) existed in NPCs. In addition, the p38MAPK signaling pathways were examined. The role of TAK-715 in vivo was determined by acupuncture-induced intervertebral disc degeneration. Following an intradiscal injection of TAK-715, MRI and a histopathological analysis were conducted to assess the degree of degeneration. Results IL-1β-induced apoptosis was alleviated by TAK-715 in vitro, and antiapoptotic proteins were upregulated. Furthermore, TAK-715 blocked IL-1β-induced inflammatory mediator production (COX-2) and inflammatory cytokine production (HMGB1) and degraded the ECM (collagen II, MMP9, ADAMTS5, and MMP3). By inhibiting the phosphorylation of p38, TAK-715 exerted its effects. In a rat tail model, TAK-715 ameliorates puncture-induced disc degeneration based on MRI and histopathology evaluations. Conclusion TAK-715 attenuated intervertebral disc degeneration in vitro and in vivo, suggesting that it might be an effective treatment for IDD.

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“…LUM is an important ECM glycoprotein in human cartilage tissue and is highly expressed in nucleus pulposus specimens from patients with lumbar disc herniation. 63 Li et al 64 showed high expression of LUM in IDD, and LUM knockdown effectively attenuated tumour necrosis factor (TNF)-α-induced inflammatory response, cell cycle arrest, and cellular senescence. COL2A1 is a major component of type II collagen and plays an important role in maintaining the gel-like properties of nucleus pulposus tissues.…”

Section: Discussionmentioning

confidence: 99%

Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration

Zhang,

Li,

Luo

et al. 2023

Bone Joint Res

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AimsThis study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).MethodsThe gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.ResultsA total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD.ConclusionThe findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.Cite this article: Bone Joint Res 2023;12(9):522–535.

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Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression

Abstract: silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating

Cited by 10 publications

References 37 publications

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis

Potential causal association between leisure sedentary behaviors and osteoporosis: A two-sample Mendelian randomization analysis

TAK-715 alleviated IL-1β-induced apoptosis and ECM degradation in nucleus pulposus cells and attenuated intervertebral disc degeneration ex vivo and in vivo

Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration

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