Protective effect of p53 on the viability of intervertebral disc nucleus pulposus cells under low glucose condition

Xiong, Xuming; Dai, Libing; Liang, Weiguo; Zhang, Jinli; Qin, Shengnan; Cao, Wenjuan; Ye, Dongping; Peng, Liang; Liu, Zhihe

doi:10.1016/j.bbrc.2017.07.055

Cited by 8 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p53 can protect NP cells against cellular damage by inducing antiapoptotic and antioxidant genes [ 45 , 46 ]. REDD1 has been identified as a direct transcriptional target gene of p53, a consensus p53 family binding element found in the REDD1 promoter area.…”

Section: Discussionmentioning

confidence: 99%

The REDD1/TXNIP Complex Accelerates Oxidative Stress‐Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

Yin

Wang

Das

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

The REDD1/TXNIP Complex Accelerates Oxidative Stress‐Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

Yin

Wang

Das

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…However, whether p53 pathway affects the degeneration process of NPCs remains controversial. Some believe that p53 has a protective effect on NPCs [30], while others have found that p53 is involved in the degradation and apoptosis of NPCs [31,32]. By overexpressing exogenous p53 in NPCs, we found that p53 significantly reduced the protein and mRNA levels of degeneration-associated factors, including aggrecan and collagen II, suggesting that p53 can promote the degeneration of NPCs.…”

Section: Discussionmentioning

confidence: 58%

Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway

Cheng

Yuan

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo. We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway.

show abstract

“…[102][103][104][105][106][107][108][109] p53 (encoded by TP53) is a mediator of senescence, oxidative stress response, apoptosis, and inflammation in IVD cells and is implicated in neovascularization and infiltration associated with IDH pathogenesis; furthermore, p53 may have potential as a therapeutic target for IDH treatment. [110][111][112][113][114][115][116][117] Aberrant activity of epidermal growth factor receptor (encoded by EGFR) is reported in degenerative IVDs and its inhibition may suppress the degeneration of IVDs and ameliorate IDH. 118,119 IL-1β (encoded by IL1B) is an IDH-associated proinflammatory cytokine, and its genetic variability may influence the clinical outcome of patients with IDH.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacological Dissection of the Mechanisms of Eucommiae Cortex-Achyranthis Radix Combination for Intervertebral Disc Herniation Treatment

Lee¹,

Kang

Jung

et al. 2021

Natural Product Communications

View full text Add to dashboard Cite

Eucommiae cortex (EC) and Achyranthis radix (AR) are herbal medicines widely used in combination for the treatment of intervertebral disc herniation (IDH). The mechanisms of action of the herbal combination have not been understood from integrative and comprehensive points of view. By adopting network pharmacological methodology, we aimed to investigate the pharmacological properties of the EC-AR combination as a therapeutic agent for IDH at a systematic molecular level. Using the pharmacokinetic information for the chemical ingredients of the EC-AR combination obtained from the comprehensive herbal drug-associated databases, we determined its 31 bioactive ingredients and 68 IDH-related therapeutic targets. By analyzing their enrichment for biological functions, we observed that the targets of the EC-AR combination were associated with the regulation of angiogenesis; cytokine and chemokine activity; oxidative and inflammatory stress responses; extracellular matrix organization; immune response; and cellular processes such as proliferation, apoptosis, autophagy, differentiation, migration, and activation. Pathway enrichment investigation revealed that the EC-AR combination may target IDH-pathology-associated signaling pathways, such as those of cellular senescence and chemokine, neurotrophin, TNF, MAPK, toll-like receptor, and VEGF signaling, to exhibit its therapeutic effects. Collectively, these data provide mechanistic insights into the pharmacological activity of herbal medicines for the treatment of musculoskeletal diseases such as IDH.

show abstract

Protective effect of p53 on the viability of intervertebral disc nucleus pulposus cells under low glucose condition

Cited by 8 publications

References 34 publications

The REDD1/TXNIP Complex Accelerates Oxidative Stress‐Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

The REDD1/TXNIP Complex Accelerates Oxidative Stress‐Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway

Network Pharmacological Dissection of the Mechanisms of Eucommiae Cortex-Achyranthis Radix Combination for Intervertebral Disc Herniation Treatment

Contact Info

Product

Resources

About