Bromodomain-containing protein 7 regulates matrix metabolism and apoptosis in human nucleus pulposus cells through the BRD7-PI3K-YAP1 signaling axis

Li, Shuangxing; Huang, Zhengqi; Zhu, Yuanxin; Yan, Jiansen; Li, Jun; Chen, Jiancong; Zhou, Jie; Zhang, Yangyang; Chen, Weijian; Xu, Kecheng; Ye, Wei

doi:10.1016/j.yexcr.2021.112658

Cited by 8 publications

(4 citation statements)

References 47 publications

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“…Recent studies have shown that, in addition to apoptosis, pyroptosis is a crucial type of cell death associated with disc degeneration ( Li et al, 2021 ). One study demonstrated that biomarkers of pyroptotic cell death were elevated in degenerative NP tissues compared with normal NP tissues ( Xu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Induces Pyroptosis and Matrix Degradation via mSREBP1-Driven Endoplasmic Reticulum Stress in Intervertebral Disc Degeneration

Yan

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Intervertebral disc degeneration (IDD) is closely associated with low back pain, but its underlying mechanism remains unclear. Cholesterol is an essential nutrient in mammalian cells. Alterations in cholesterol levels lead to impairments in cell physiology, such as cell proliferation and signal transduction. Previous clinical studies demonstrated that hypercholesterolemia could be a potential risk factor for IDD, but how cholesterol induces IDD remains unknown. The current study aimed to explore the regulatory role of cholesterol in IDD development and the potential underlying mechanisms. It was found that different forms of cholesterol levels were elevated in degenerative nucleus pulposus (NP) tissues in both humans and Sprague–Dawley rats. Rats fed a high cholesterol diet (HCD) exhibited degenerative features in the lumbar intervertebral disc compared with those fed a standard diet. Interestingly, this effect could be abolished by cholesterol-lowering drug atorvastatin. In NP cells treated with TNF-α and IL-1β, a significantly higher level of cholesterol was observed. These results suggested a pivotal role of cholesterol in the progression of IDD. We also observed accelerated pyroptosis in NP cells and extracellular matrix (ECM) degradation in the rat NP cells treated with exogenous cholesterol. We further demonstrated that endoplasmic reticulum stress was responsible for cholesterol-induced pyroptosis and ECM degradation. Moreover, RNA-seq analysis revealed that the mature form of SREBP1 (mSREBP1), an important regulator of lipid metabolism, is involved in regulating endoplasmic reticulum stress in knockdown experiments. In conclusion, this study demonstrated that cholesterol could induce pyroptosis in NP cells and ECM degradation by activating endoplasmic reticulum stress through stimulating mSREBP1 in IDD.

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Section: Discussionmentioning

confidence: 99%

Cholesterol Induces Pyroptosis and Matrix Degradation via mSREBP1-Driven Endoplasmic Reticulum Stress in Intervertebral Disc Degeneration

Yan

Zhang

et al. 2022

Front. Cell Dev. Biol.

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“…In addition, activated YAP promoted choline metabolism by inducing expression of those genes involved in apical extrusion during cell competition [89]. Moreover, YAP overexpression promoted the synthesis of ECM components such as aggrecan, type II collagen, and sulfated glycosaminoglycan [90].…”

Section: Yap/taz Is Essential For Liver Metabolismmentioning

confidence: 99%

Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction

Shu

Zhang

et al. 2023

IJMS

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Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis.

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“…Intervertebral disc degeneration (IDD) is considered one of the main causes of LBP [1]. IDD is an irreversible pathological process characterized by degradation of the extracellular matrix (ECM), dehydration and proteoglycan loss, inflammation, cell senescence and cell death in the nucleus pulposus (NP) [5][6][7]. The anatomic and biochemical changes during IDD further subject the spine to the loss of mechanical stability and pose threat to adjacent tissues including nerves, ligaments and muscles [8].…”

Section: Introductionmentioning

confidence: 99%

The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China

et al. 2023

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Background Intervertebral disc degeneration (IDD) and vertebral endplate Modic changes (MCs) are common lumbar degenerative phenotypes related to low back pain (LBP). Dyslipidemia has been linked to LBP but its associations with IDD and MCs have not been fully elucidated. The present study aimed to address the possible link between dyslipidemia, IDD and MCs in the Chinese population. Methods 1035 citizens were enrolled in the study. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were collected. IDD was evaluated based on the Pfirrmann grading system and subjects with an average grade ≥ 3 were defined as having degeneration. MCs were classified into typical types 1, 2 and 3. Covariables, including age, sex, BMI and fasting plasma glucose, were included for the adjustment of the logistic analyses. Results The degeneration group included 446 subjects while the nondegeneration group included 589 subjects. The degeneration group had significant higher levels of TC and LDL-C (p < 0.001) whereas TG and HDL-C were not significantly different between the two groups. TC and LDL-C concentrations were significantly positively correlated with average IDD grades (p < 0.001). Multivariate logistic regression revealed that high TC (≥ 6.2 mmol/L, adjusted OR = 1.775, 95% CI = 1.209–2.606) and high LDL-C (≥ 4.1 mmol/L, adjusted OR = 1.818, 95% CI = 1.123–2.943) were independent risk factors for IDD. Type 1 MC presented in 84 (8.12%) subjects, type 2 MC presented in 244 (23.57%) subjects, type 3 MC presented in 27 (2.61%) subjects and no MC was observed in the remaining 680 (65.70%) subjects. The type 2 MC group demonstrated a higher level of TC, but the association between serum lipids and MCs could not be confirmed in further multivariate logistic regression. Conclusions High TC (≥ 6.2 mmol/L) and LDL-C (≥ 4.1 mmol/L) concentrations were independent risk factors for IDD for citizens in China. However, the association between dyslipidemia and MCs could not be determined. The effect of excess serum cholesterol may be critical for IDD and cholesterol lowering treatment may provide new opportunities in the management of lumbar disc degeneration.

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Bromodomain-containing protein 7 regulates matrix metabolism and apoptosis in human nucleus pulposus cells through the BRD7-PI3K-YAP1 signaling axis

Cited by 8 publications

References 47 publications

Cholesterol Induces Pyroptosis and Matrix Degradation via mSREBP1-Driven Endoplasmic Reticulum Stress in Intervertebral Disc Degeneration

Cholesterol Induces Pyroptosis and Matrix Degradation via mSREBP1-Driven Endoplasmic Reticulum Stress in Intervertebral Disc Degeneration

Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction

The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China

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