Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction

Guo, Daru; Cheng, Kang; Song, Chao; Liu, Fei; Cai, Weiye; Chen, Jingwen; Mei, Yongliang; Zhou, Daqian; Gao, Silong; Wang, Guoyou; Liu, Zongchao

doi:10.1016/j.intimp.2023.110844

Cited by 4 publications

(4 citation statements)

References 43 publications

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“…As a complementary therapy, DHJSD is widely for the management of bone and joint diseases in China; however, its exact mechanism has not been completely elucidated. Existing studies have confirmed that DHJSD regulates inflammatory factors, reduces apoptosis and pyroptosis of nucleus pulposus cells, and inhibits extracellular matrix degradation [9][10][11][12], indicating the multiple mechanisms of action of DHJSD in osteoarthritis (OA).…”

Section: Methodsmentioning

confidence: 99%

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Wang,

Zhou,

Gao

et al. 2024

PLoS ONE

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Background Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. Objective This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. Methods A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. Results Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. Conclusion DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.

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Section: Methodsmentioning

confidence: 99%

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Wang,

Zhou,

Gao

et al. 2024

PLoS ONE

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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- S7; Figure 9B). We can see from the WB results that CASP3 is different in the model and control groups in protein levels, but the statistical significance is less significant.…”

Section: Results Of Hub Gene Validationmentioning

confidence: 95%

“…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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“… 80 Duhuo Jisheng Decoction (DHJSD) effectively attenuates LPS-induced disc inflammatory response and further inhibits NLRP3 expression, which may inhibit NPC pyroptosis via the SDF-1/CXCR4-NF-kB-NLRP3 axis. 81 Research into cell therapy is an important modality in the treatment of IDD. A systematic review has shown that basic experiments confirm that SCs are effective in the treatment of IDD, but reliable clinical studies are lacking.…”

Section: Therapeutic Role Of Immune Cells In Iddmentioning

confidence: 99%

Analysis of global research hotspots and trends in immune cells in intervertebral disc degeneration: A bibliometric study

Wang,

Mi,

Chen

et al. 2023

Human Vaccines & Immunotherapeutics

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Intervertebral disc degeneration is an important pathological basis for spinal degenerative diseases. The imbalance of the immune microenvironment and the involvement of immune cells has been shown to lead to nucleus pulposus cells death. This article presents a bibliometric analysis of studies on immune cells in IDD in order to clarify the current status and hotspots. We searched the WOSCC, Scopus and PubMed databases from 01/01/2001 to 08/03/2023. We analyzed and visualized the content using software such as Citespace, Vosviewer and the bibliometrix. This study found that the number of annual publications is increasing year on year. The journal study found that Spine had the highest number of articles and citations. The country/regions analysis showed that China had the highest number of publications, the USA had the highest number of citations and total link strength. The institutional analysis found that Shanghai Jiao Tong University and Huazhong University of Science Technology had the highest number of publications, Tokai University had the highest citations, and the University of Bern had the highest total link strength. Sakai D and Risbud MV had the highest number of publications. Sakai D had the highest total link strength, and Risbud MV had the highest number of citations. The results of the keyword analysis suggested that the current research hotspots and future directions continue to be the study of the mechanisms of immune cells in IDD, the therapeutic role of immune cells in IDD and the role of immune cells in tissue engineering for IDD.

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Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction

Cited by 4 publications

References 43 publications

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

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

Analysis of global research hotspots and trends in immune cells in intervertebral disc degeneration: A bibliometric study

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