Aucubin inhibits IL‐1β‐ or TNF‐α‐induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR‐140‐5p/CREB1 axis

Yang, Shaofeng; Li, Linghui; Zhu, Li; Zhang, Chao; Li, Zhaoyong; Guo, Yantao; Nie, Ying; Luo, Zhenhua

doi:10.1002/jcp.28044

Cited by 29 publications

(18 citation statements)

References 59 publications

(82 reference statements)

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“…Concerning sources of IL-1β, the activation of the complement system, and subsequent generation of anaphylatoxins C3a and C5a, has been shown to promote its production [31,32]. For instance, C3a is known to increase IL-1β secretion in human tenocytes [33] and monocytes and regulates the inflammasome activation [34].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue

et al. 2021

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Purpose Formation of terminal complement complex (TCC), a downstream complement system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate complement activation during disc degeneration (DD). This study investigated a possible involvement of the pro-inflammatory cytokine interleukin-1β (IL-1β) and the lysosomal protease cathepsin D (CTSD). Methods Disc biopsies were collected from patients suffering from DD (n = 43) and adolescent idiopathic scoliosis (AIS, n = 13). Standardized tissue punches and isolated cells from nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) were stimulated with 5% human serum (HS) alone or in combination with IL-1β, CTSD or zymosan. TCC formation and modulation by the complement regulatory proteins CD46, CD55 and CD59 were analysed. Results In DD tissue cultures, IL-1β stimulation decreased the percentage of TCC + cells in AF and EP (P < 0.05), whereas CTSD stimulation significantly increased TCC deposition in NP (P < 0.01) and zymosan in EP (P < 0.05). Overall, the expression of CD46, CD55 and CD59 significantly increased in all isolated cells during culture (P < 0.05). Moreover, cellular TCC deposition was HS concentration dependent but unaffected by IL-1β, CTSD or zymosan. Conclusion These results suggest a functional relevance of IL-1β and CTSD in modulating TCC formation in DD, with differences between tissue regions. Although strong TCC deposition may represent a degeneration-associated event, IL-1β may inhibit it. In contrast, TCC formation was shown to be triggered by CTSD, indicating a multifunctional involvement in disc pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1β and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue

et al. 2021

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“…Human NP cells (ScienCell, USA) was cultured at specific medium containing 10% fetal bovine serum (FBS), 1% NP cell growth supplement and 1% penicillin/streptomycin in 5% CO 2 at 37°C (ScienCell, USA). When cells adhered to the wall up to 80%, IL-1β (Reprotech, USA) was added into the medium to induce degeneration of NP cells for 24 hours, the concentration of which was 10 ng/mL as described in previous studies [ 7 , 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…And matrix lysin protease MMP-3 can hydrolyze a variety of substrates including proteoglycan, gelatin, collagen, and so on. Pro-inflammatory factors can induce the production of MMPs and ADAMTSs to contribute to disc degeneration [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

et al. 2020

Med Sci Monit

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Background Disc degeneration is characterized partly by the degradation in the extracellular matrix (ECM) and excess apoptosis of nucleus pulposus (NP) cells. NLRX1 (nucleotide-binding, leucine-rich repeat containing X1) is different from the other nucleotide-binding-domain and leucine-rich-repeat proteins and mainly located to the mitochondrial. It negatively regulates NF-κB (nuclear factor kappa B) and apoptosis inhibition. However, how NLRX1 is regulated and exerts effects in disc degeneration is unclear. Thus, the study aimed to analyze the effects of NLRX1 on NP cells. Material/Methods NLRX1 expression was detected in interleukin (IL)-1β-induced NP cells by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Then, NLRX1 was overexpressed in IL-1β-induced NP cells to detect apoptosis-related proteins and the extracellular matrix (ECM) by western blot, along with the detection of apoptosis levels using flow cytometry. StarBase predicted miR-423-5p target 3′UTR of NLRX1. Dual luciferase reporter assay showed that miR-423-5p could bind to the 3′UTR of NLRX1. Besides, miR-423-5p significantly affected NLRX1 levels detected by qRT-qPCR. Results The miR-423-5p overexpression markedly, and negatively regulated the protective effects of NLRX1 on IL-1β induced NP cells. Thus, our results suggested that miR-423-5p mediated the regulation of NLRX1 to affect apoptosis and ECM levels in IL-1β induced NP cells. Conclusions miR-423-5p and NLRX1 could be potential therapeutic targets for patients with disc degeneration.

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“…Reversing or alleviating ECM loss is crucial for IDD. Aucubin, a compound found in traditional Chinese medicines, was reported to play a key role in the regulation of the ECM (90). In IDD, the increased release of pro-inflammatory factors by NPCs can cause the degradation of the ECM.…”

Section: Mirnas and Ecm Remodelingmentioning

confidence: 99%

Role of microRNAs in intervertebral disc degeneration (Review)

et al. 2021

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The incidence of lower back pain caused by intervertebral disc degeneration (IDD) is gradually increasing. IDD not only affects the quality of life of the patients, but also poses a major socioeconomic burden. There is currently no optimal method for delaying or reversing IDD, mainly due to its unknown pathogenesis. MicroRNAs (miRNAs/miRs) participate in the development of a number of diseases, including IDD. Abnormal expression of miRNAs in the intervertebral disc is implicated in various pathological processes underlying the development of IDD, including nucleus pulposus (NP) cell (NPC) proliferation, NPC apoptosis, extracellular matrix remodeling, inflammation and cartilaginous endplate changes, among others. The focus of the present review was the advances in research on the involvement of miRNAs in the mechanism underlying IDD. Further research is expected to identify markers for early diagnosis of IDD and new targets for delaying or reversing IDD.

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Aucubin inhibits IL‐1β‐ or TNF‐α‐induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR‐140‐5p/CREB1 axis

Cited by 29 publications

References 59 publications

Interleukin-1β and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue

Interleukin-1β and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue

MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

Role of microRNAs in intervertebral disc degeneration (Review)

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