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, Kun; Yao, Dengbo; Li, Yuxi; Li, Ming; Zeng, Weike; Liao, Zhuangyao; Chen, Engming; Lu, Sha; Su, Kaihui; Che, Zhen; Liang, Yuhan; Wang, Peng; Huang, Lin

doi:10.1186/s13075-023-03028-4

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Catabolic enzymes, such as MMP3, are closely related to the ECM catabolism of NP cells (Wang et al . 2023 ). So, the expression of MMP3 and ECM-related proteins (aggrecan and collagen II) was detected by qRT-PCR and Western blot analysis to assess the catabolic activity of the NP cells.…”

Section: Resultsmentioning

confidence: 99%

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1β-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway

Yu,

Hao,

Ren

et al. 2024

In Vitro Cell.Dev.Biol.-Animal

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The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1β-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1β, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1β to simulate IVDD environment and divided into the control group, IL-1β group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway–related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1β, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1β-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1β-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1β-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway

Yu,

Hao,

Ren

et al. 2024

In Vitro Cell.Dev.Biol.-Animal

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“… 14 , 15 Therefore, it is crucial to regulate the release of inflammatory factors and inhibit oxidative stress levels within the IVD for both prevention and treatment of IDD. To simulate the microenvironment of IDD characterized by inflammation and oxidative stress, we induced NPCs with IL-1β to establish an IDD model, 16 , 17 and intervened with SN to investigate its potential in inhibiting IDD. Our findings suggest that IL-1β not only triggers an inflammatory response in NPCs, resulting in a significant upregulation of IL-1β, IL-6, IL-17 and TNF-α synthesis, but also induces ROS accumulation, enhanced apoptosis, reduced proliferative activity and impaired wound healing capacity in NPCs.…”

Section: Discussionmentioning

confidence: 99%

Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways

Lu,

Zhang,

et al. 2023

JIR

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Purpose To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). Methods The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1β to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1β. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1β. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques. Results IL-1β significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1β injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes. Conclusion SN can prevent IL-1β-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway.

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“…IVDD originates from a multifaceted combination of genetic predispositions, mechanical stressors, and environmental influences. Among these, inflammation is progressively gaining recognition as a critical orchestrator, steering the path towards degenerative processes 5 , 6 . IL-1βis a pro-inflammatory cytokine produced by activated macrophages and is involved in various cellular activities, including cell proliferation, differentiation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

Sun,

Zhu,

Sun

et al. 2023

Int. J. Med. Sci.

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Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro . Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD.

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

Cited by 5 publications

References 43 publications

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1β-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1β-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway

Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

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