SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration

Wu, Zhi-Xi; Chen, Yajun; Zhang, Guangzhi; Xie, Qiqi; Wang, Ke-Ping; Yang, Xin; Liu, Tai-Cong; Wang, Zhiqiang; Zhao, Guanghai; Zhang, Haihong

doi:10.1007/s10495-022-01707-2

Cited by 7 publications

(5 citation statements)

References 50 publications

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“…IDD is a common spinal degenerative disease in orthopedics, and its incidence is positively correlated with age. Although many studies have revealed relevant mechanisms of IDD development, the underlying mechanisms are still not fully understood [ 6 , 29 ]. In recent years, the role of cellular senescence in the occurrence and development of IDD has been more extensively investigated [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

付洛安

2023

BMC Musculoskelet Disord

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Intervertebral disc degeneration (IDD) is considered one of the main causes of low back pain and lumbar disc herniation. Various studies have shown that disc cell senescence plays a critical role in this process. however, its role in IDD is yet unclear. In this study, we explored the role of senescence-related genes (SR-DEGs) and its underlying mechanism in IDD. A total of 1325 differentially expressed genes (DEGs) were identified using Gene Expression Omnibus (GEO) database GSE41883. 30 SR-DEGs were identified for further functional enrichment and pathway analysis, and two hub SR-DEGs (ERBB2 and PTGS2) were selected to construct transcription factor (TF)–gene interaction and TF-miRNA coregulatory networks, and 10 candidate drugs were screened for the treatment of IDD. Last but not least, in vitro experiments show that ERBB2 expression decreased and PTGS2 expression increased in human nucleus pulposus (NP) cell senescence model treated with TNF-α. After lentivirus-mediated overexpression of ERBB2, the expression of PTGS2 decreased and the senescence level of NP cells decreased. Overexpression of PTGS2 reversed the anti-senescence effects of ERBB2. The findings in this study suggested that ERBB2 overexpression further reduced NP cell senescence by inhibiting PTGS2 levels, which ultimately alleviated IDD. Taken together, our findings provide new insights into the roles of senescence-related genes in IDD and highlight a novel target of ERBB2-PTGS2 axis for therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

付洛安

2023

BMC Musculoskelet Disord

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“…This could be a result of IVDD-induced apoptosis reducing the number of NP cells, impairing normal cell function, and increasing the secretion of in ammatory factors, which speed up the apoptosis of nearby cells and the breakdown of the ECM. [37].…”

Section: Discussionmentioning

confidence: 99%

Intervertebral disc degeneration induced by lumbar instability followed by a maintained standing posture: An in vivo rabbit model

Chen

Zhou

Liu

et al. 2023

Preprint

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Background: Intervertebral disc degeneration (IVDD) is a major clinical cause of low back pain. The ideal animal model should induce a degenerative process and morphological properties similar to those that occur in human IVDD. We established an IVDD model by maintaining rabbits in an upright posture after inducing lumbar instability to better simulate human IVDD. Methods: IVDD was induced in rabbits by severing the supraspinous and interspinous ligaments of the L5-6 and L6-7 segments and maintaining rabbits in an upright position for 12 weeks. After 8 and 12 weeks, X-ray and magnetic resonance imaging (MRI) were analysed. Disc pathological changes at 12 weeks were detected using haematoxylin and eosin staining, safranin-O-fast green staining, and immunohistochemistry. Results: In the model group, L6-7 and L7-S1 segment disc degeneration was aggravated at 12 weeks. MRI analysis showed that at 12 weeks, the L6-7 and L7-S1 intervertebral disc nucleus pulposus (NP) signal intensity was significantly decreased compared with that of the control group. Compared with the control group, the model group had obvious histomorphological degeneration at 12 weeks, and significantly different histological scores. Model group immunohistochemistry results at 12 weeks showed that the NP type II collagen content was decreased and the type I collagen content was increased. Conclusions: An animal model of early lumbar disc degeneration was successfully established by maintaining the rabbit lumbar spine in an upright position for an extended period after inducing lumbar instability. This model will be useful for studying the degenerative process of intervertebral discs under mechanical stimulation.

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“…One Step TUNEL Apoptosis Assay Kit (Beyotime) was applied to measure cell apoptosis according to the manufactures protocol [ 36 ]. Briefly, LUAD cells were incubated with PBS containing 0.3% Triton X-100 for 10 min and then incubated with 0.3% H 2 O 2 in PBS for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of ubiquitin-conjugating enzyme E2T (UBE2T) suppresses lung adenocarcinoma progression via targeting fibulin-5 (FBLN5)

Li¹,

Xiao²,

Lü

2022

Bioengineered

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Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Accumulating evidence has displayed that UBE2T is related to tumor progression. However, its role in LUAD has not been fully elucidated. The expression of UBE2T was detected in LUAD tissues by qRT-PCR, western blotting, and immunohistochemistry. UBE2T shRNAs were transfected into LUAD cells to analyze the consequent alteration in function through CCK-8 assay, Edu assay, transwell assay, and TUNEL staining. The potential mechanism of UBE2T was analyzed through GEPIA and verified using ChIP, EMSA, and GST pull-down assays. Furthermore, a xenograft mouse model was used to assess UBE2T function in vivo . Results showed that UBE2T level was significantly elevated in LUAD tissues and high UBE2T expression was associated with poor overall survival and disease-free survival. Results from the loss-of-function experiments in vitro showed that UBE2T modulated LUAD cell proliferation, migration, invasion, and apoptosis. The mechanism analysis demonstrated that silence of UBE2T increased FBLN5 expression and inhibited the activation of p-ERK, p-GSK3β, and β-catenin. Moreover, following knockdown of UBE2T, the cell proliferation, migration, and invasion were decreased, and sh-FBLN5 partially reverse the decrease. In in vivo experiments, it was found that UBE2T knockdown inhibits the tumor growth in LUAD. Immunohistochemically, there was a reduction in Ki67 and an increase in FBLN5 in UBE2T shRNA-treated tumor tissues. In conclusion, UBE2T might be a potential biomarker of LUAD, and targeting the UBE2T/FBLN5 axis might be a novel treatment strategy for LUAD.

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SKI knockdown suppresses apoptosis and extracellular matrix degradation of nucleus pulposus cells via inhibition of the Wnt/β-catenin pathway and ameliorates disc degeneration

Cited by 7 publications

References 50 publications

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells

Intervertebral disc degeneration induced by lumbar instability followed by a maintained standing posture: An in vivo rabbit model

Knockdown of ubiquitin-conjugating enzyme E2T (UBE2T) suppresses lung adenocarcinoma progression via targeting fibulin-5 (FBLN5)

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