LncRNA TUG1 Promotes the Intervertebral Disc Degeneration and Nucleus Pulposus Cell Apoptosis Though Modulating miR-26a/HMGB1 Axis and Regulating NF-κB Activation

Dong, Yixiao; Xiao, Ting‐Hui; Yu, Bin; Zhao, Hong

doi:10.2139/ssrn.3493212

Cited by 14 publications

(11 citation statements)

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“…The results of behavior test showed that L. paracasei S16 treatment had alleviating action on LDH mice, which is characterized by the increased mechanical withdrawal and thermal withdraw. It has been reported that LDH exhibited increased cell apoptosis and decreased cell proliferation ( 19 , 20 ). Thus, in this study, we examined the effects of L. paracasei S16 treatment on the expressions of cell proliferation-related markers.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota

Wang

Chen

et al. 2021

Front. Nutr.

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Lumbar disc herniation (LDH) is a common cause for low back pain. In this study, we aimed to explore the effects of a specific Lactobacillus paracasei (L. paracasei), L. paracasei S16, on the symptoms of LDH using a mouse model of LDH. The results showed that L. paracasei S16 treatment improved the behavior, increased the cell proliferation, and decreased the apoptosis in LDH mice. Moreover, L. paracasei S16 treatment alleviated the aberrant inflammation response in the LDH mice, which is characterized by the decreased anti-inflammatory cytokines, increased pro-inflammatory cytokines, and decreased percentage of Th1 and Th2 cells and Th17/Treg ratio. 16S rRNA sequencing results showed that the LDH mice treated with L. paracasei S16 have higher relative abundance of Lachnospiraceae and Ruminococcaceae and lower abundance of Lactobacillaceae than mice in the LDH group. Additionally, the serum metabolites involved in the linoleic acid metabolism, alanine. aspartate, and glutamate, glycerophospholipid, and TCA cycle were significantly decreased and the metabolite involved in purine metabolism was significantly increased after the L. paracasei S16 treatment in the LDH mice. These results showed that administration of L. paracasei S16 can improve inflammation response, alter gut microbiota, and modulate serum metabolomics in a mouse model of LDH.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota

Wang

Chen

et al. 2021

Front. Nutr.

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“…Previous convincing experimental data have demonstrated that engagement of Fas with FasL increases RelA/P65 phosphorylation, indicating NF- κ B activation [ 37 , 38 ]. On the other hand, other compelling data have shown that NF- κ B enhances cleavage of caspase 3 to trigger apoptosis in NPCs [ 39 , 40 ]. We can draw from these reports that the elevation in Fas consumption due to higher combination of LC3B and Fas leads to obstruction of NF- κ B activation and ultimately inhibition of cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 Attenuates Apoptosis of Nucleus Pulposus Cells by Targeting Interactions between LC3B and Fas under High‐Magnitude Compression

Zhuo

Wang

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mechanical overloading-induced nucleus pulposus cell (NPC) apoptosis plays a core role in the pathogenesis of intervertebral disc degeneration. In this study, we investigated the involvement of mammalian silent information regulator 2 homolog (SIRT1) in NPC apoptosis under high-magnitude compression. Our results showed that high-magnitude compression aggravated cellular apoptosis and attenuated the expression levels of SIRT1 and microtubule-associated protein-1 light chain-3B (LC3B) in rat NPCs in a three-dimensional (3D) cell culture model and an in vivo rat tail compression model, whereas SIRT1 overexpression in NPCs partially reversed these indicators. Moreover, SIRT1 overexpression increased the formation of the LC3B/Fas complex, alleviated activation of the NF-κB pathway, and reduced NPC apoptosis. Finally, downregulation of LC3B partially activated the NF-κB pathway and aggravated NPC apoptosis. Overall, upregulation of SIRT1 increases formation of the LC3B/Fas complex, which contributes to suppression of NPC apoptosis by inhibiting the NF-κB pathway under high compressive stress.

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“…We further found binding sites between GAS5 and miR-26a-5p, and between miR-26a-5p and PTEN. miR-26a is notably downregulated in human degenerative NPCs ( 45 ). PTEN can promote IDD by regulating the behaviors of degenerative NPCs ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA GAS5 as miR-26a-5p Sponge Regulates the PTEN/PI3K/Akt Axis and Affects Extracellular Matrix Synthesis in Degenerative Nucleus Pulposus Cells in vitro

Tan

Xie²,

Yuan³

et al. 2021

Front. Neurol.

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The role of lncRNA growth arrest specific 5 (GAS5) in degenerative nucleus pulposus cell (NPC) apoptosis has been reported, but the mechanism of GAS5 in extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IDD) remains unknown. We aimed to investigate the mechanism of GAS5 in ECM synthesis in degenerative NPCs. GAS5 expression was measured in degenerative NPCs (CP-H170) and normal NPCs (CP-H097). siRNA-mediated GAS5 knockdown was transfected to NPCs to detect cell viability and the expression of ECM-related genes (Collagen II, aggrecan, Collagen I, and MMP-3). Subcellular localization of GAS5 was analyzed. The downstream gene and pathway of GAS5 in degenerative NPCs were explored. As our results indicated, lncRNA GAS5 was upregulated in degenerative NPCs. Silencing GAS5 improved the viability of degenerative NPCs and increased ECM synthesis. GAS5 was mainly located in the cytoplasm of NPCs. LncRNA GAS5 sponged miR-26a-5p to regulate PTEN. Overexpression of miR-26a-5p promoted ECM synthesis in degenerative NPCs. Akt inhibitor LY294002 reversed the promotion of silencing GAS5 on ECM synthesis of degenerative NPCs. In conclusion, lncRNA GAS5 sponged miR-26a-5p to upregulate PTEN and inhibit the PI3K/Akt pathway, thus inhibiting ECM synthesis of degenerative NPCs.

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LncRNA TUG1 Promotes the Intervertebral Disc Degeneration and Nucleus Pulposus Cell Apoptosis Though Modulating miR-26a/HMGB1 Axis and Regulating NF-κB Activation

Cited by 14 publications

References 0 publications

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota

Lactobacillus paracasei S16 Alleviates Lumbar Disc Herniation by Modulating Inflammation Response and Gut Microbiota

SIRT1 Attenuates Apoptosis of Nucleus Pulposus Cells by Targeting Interactions between LC3B and Fas under High‐Magnitude Compression

LncRNA GAS5 as miR-26a-5p Sponge Regulates the PTEN/PI3K/Akt Axis and Affects Extracellular Matrix Synthesis in Degenerative Nucleus Pulposus Cells in vitro

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