The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

Tian, DaSheng; Li, Jianjun; Chen, Lei; Zhu, Bin; Jing, Juehua

doi:10.1186/s13018-020-1551-9

Cited by 24 publications

(24 citation statements)

References 39 publications

(40 reference statements)

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“…Consistently, IGF-1 significantly decreased Col-X and LY294002 increased Col-X. Tian et al showed that in anoxic and nutritionally deprived environments, the Col-II gene expression significantly reduced which IGF-1 almost helped return to the normal and LY294002 worsened the situation in NP mesenchymal stem cells [ 28 ]. Our study confirmed that in normal conditions, NPCs also lose Col-II and obtain Col-X due to antagonizing P13K/AKT pathway.…”

Section: Discussionmentioning

confidence: 95%

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Xiao¹,

Teng

Xu³

et al. 2021

BioMed Research International

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Objective. To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells. Methods. Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 μM, 10 μM, and 20 μM). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13. Results. PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells. Conclusion. The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.

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Section: Discussionmentioning

confidence: 95%

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Xiao¹,

Teng

Xu³

et al. 2021

BioMed Research International

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“…For example, under oxidative damage, Resveratrol increased ECM synthesis of NPCs by enhancing autophagy through PI3K/AKT pathway [28] . Further study con rmed that PI3K/AKT pathway had protective effects on human nucleus pulposus-derived mesenchymal stem cells under hypoxia and nutrition de ciency [29] . Conversely, PTEN, the only known lipid phosphatase counteracting the PI3K/AKT pathway, promoted intervertebral disc degeneration by regulating nucleus pulposus cell behaviors [30] .…”

Section: 2mentioning

confidence: 88%

Identification of Key Genes and Pathways Associated With Pathogenesis of Intervertebral Disc Degeneration by Integrated miRNA-mRNA Network Analysis

Lan¹,

Li²,

Shen³

et al. 2021

Preprint

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Background: Intervertebral disc degeneration (IDD) is one of the most common cause of low back pain. Previous studies have suggested that miRNAs are associated with the pathogenesis of IDD. However, the underlying mechanisms remain unclear based on inconsistent results of available literatures. In addition, integrated miRNA-mRNA comprehensive analysis is limited. Material/Methods: In this study, we investigated the profiles of differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) and constructed a miRNA-mRNA regulatory network. First, transcription factors and target genes of DEMIs were predicted. Then, an intersection between DEMIs predicted genes and DEGs were performed to screen out the most significant differential expressed common genes. Results: A total of 65 DEMIs and 61 common target genes were identified from datasets. Functional enrichment analysis showed that most genes were mainly involved in extracellular matrix organization and extracellular structure organization. Furthermore, DEGs were primarily enriched in PI3K−Akt signaling pathway, ECM−receptor interaction, focal adhesion and p53 signaling pathway, indicating that these pathways may be the critical pathways.Conclusions: In summary, several important miRNAs, as well as their related target genes and transcription factors in the pathogenesis of IDD were identified from our bioinformatic analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

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“…NPMSCs are the precursor of NPCs, which exist in healthy and degenerative IVD tissues, and has the potential to proliferate and differentiate into NPCs [ 17 ]. Furthermore, these cells show great potential for application in regenerative and repairing sciences [ 3 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of lentivirus-mediated growth and differentiation factor-5 transfection on differentiation of rabbit nucleus pulposus mesenchymal stem cells

Zhu

Zhao

et al. 2022

Eur J Med Res

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Background Intervertebral disc degeneration (IDD) is a natural progression of age-related processes. Associated with IDD, degenerative disc disease (DDD) is a pathologic condition implicated as a major cause of chronic lower back pain, which can have a severe impact on the quality of life of patients. As degeneration progression is associated with elevated levels of inflammatory cytokines, enhanced aggrecan and collagen degradation, and changes in the disc cell phenotype. The purpose of this study was to investigate the biological and cytological characteristics of rabbit nucleus pulposus mesenchymal stem cells (NPMSCs)—a key factor in IDD—and to determine the effect of the growth and differentiation factor-5 (GDF5) on the differentiation of rabbit NPMSCs transduced with a lentivirus vector. Methods An in vitro culture model of rabbit NPMSCs was established and NPMSCs were identified by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Subsequently, NPMSCs were randomly divided into three groups: a transfection group (the lentiviral vector carrying GDF5 gene used to transfect NPMSCs); a control virus group (the NPMSCs transfected with an ordinary lentiviral vector); and a normal group (the NPMSCs alone). FCM, qRT-PCR, and western blot (WB) were used to detect the changes in NPMSCs. Results The GDF5-transfected NPMSCs displayed an elongated shape, with decreased cell density, and significantly increased GDF5 positivity rate in the transfected group compared to the other two groups (P < 0.01). The mRNA levels of Krt8, Krt18, and Krt19 in the transfected group were significantly higher in comparison with the other two groups (P < 0.01), and the WB results were consistent with that of qRT-PCR. Conclusions GDF5 could induce the differentiation of NPMSCs. The lentiviral vector carrying the GDF5 gene could be integrated into the chromosome genome of NPMSCs and promoted differentiation of NPMSCs into nucleus pulposus cells. Our findings advance the development of feasible and effective therapies for IDD.

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The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

Cited by 24 publications

References 39 publications

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Identification of Key Genes and Pathways Associated With Pathogenesis of Intervertebral Disc Degeneration by Integrated miRNA-mRNA Network Analysis

Effect of lentivirus-mediated growth and differentiation factor-5 transfection on differentiation of rabbit nucleus pulposus mesenchymal stem cells

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