Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

Ye, Dongping; Liang, Weiguo; Dai, Libing; Yao, Yicun

doi:10.1155/2018/9405738

Cited by 11 publications

(12 citation statements)

References 35 publications

(57 reference statements)

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“…To understand the mechanism whereby mechanical loading might activate the expression of CCL2 in osteoblasts, we screened several activated kinases including FAK, JNK, p‐38, and ERK1/2, which have been previously associated with the CCL2 expression upon mechanical loading in various mechanosensitive cells 4,16,36‐38 . Results showed time‐dependent elevation of the phosphorylated ERK1/2 level in osteoblastic MC3T3‐E1 treated by mechanical loading (Figure 6A).…”

Section: Resultsmentioning

confidence: 95%

CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

et al. 2021

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It has been known that moderate mechanical loading, like that caused by exercise, promotes bone formation. However, its underlying mechanisms remain elusive. Here we showed that moderate running dramatically improved trabecular bone in mice tibias with an increase in bone volume fraction and trabecular number and a decrease in trabecular pattern factor. Results of immunohistochemical and histochemical staining revealed that moderate running mainly increased the number of osteoblasts but had no effect on osteoclasts. In addition, we observed a dramatic increase in the number of colony forming unit‐fibroblast in endosteal bone marrow and the percentage of CD45−Leptin receptor+ (CD45−LepR+) endosteal mesenchymal progenitors. Bioinformatics analysis of the transcriptional data from gene expression omnibus (GEO) database identified chemokine c‐c‐motif ligands (CCL2) as a critical candidate induced by mechanical loading. Interestingly, we found that CCL2 was up‐regulated mainly in osteoblastic cells in the tibia of mice after moderate running. Further, we found that mechanical loading up‐regulated the expression of CCL2 by activating ERK1/2 pathway, thereby stimulating migration of endosteal progenitors. Finally, neutralizing CCL2 abolished the recruitment of endosteal progenitors and the increased bone formation in mice after 4 weeks running. These results therefore uncover an unknown connection between osteoblasts and endosteal progenitors recruited in the increased bone formation induced by mechanical loading.

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Section: Resultsmentioning

confidence: 95%

CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

et al. 2021

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“…IVDD is characterized by chemokine production, extracellular matrix degradation, and cell phenotype changes [ 3 ]. Intervertebral disc degeneration was caused by synergistic effects of multiple factors, including genetic inheritance, nutritional delivery, and mechanical and inflammatory mediators [ 4 ]. Among these, the genetics play critical roles in the occurrence and progression of IVDD.…”

Section: Introductionmentioning

confidence: 99%

Expression of ANGPTL4 in Nucleus Pulposus Tissues Is Associated with Intervertebral Disc Degeneration

Liu

Xie

et al. 2021

Disease Markers

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Objective. Angiopoietin-like protein 4 (ANGPTL4), encoding a glycosylated secreted protein, has been reported to be closely related to many kinds of diseases, including diabetes, tumor, and some musculoskeletal pathologies, such as rheumatoid arthritis, osteoarthritis, and osteoporosis. The aim of the current study is to investigate the role of ANGPTL4 in intervertebral disc degeneration and analyze the association of ANGPTL4 expression with Pfirrmann grades. Methods. A total of 162 nucleus pulposus tissues were collected from lumbar intervertebral disc herniation patients undergoing interforaminal endoscopic surgery. Real-time quantitative PCR and western blot were performed to determine the mRNA and protein expression of ANGPTL4 in nucleus pulposus samples. Statistical analysis was performed to analyze the association of ANGPTL4 expression with Pfirrmann grades. Results. Based on the clinical data of 162 patients, results showed that Pfirrmann grades were significantly associated with patients’ age ( r = 0.162 , P = 0.047 ) and were not significantly associated with patients’ gender ( P > 0.05 ). RT-qPCR and western blot results showed that the mRNA ( r = 0.287 , P < 0.05 ) and protein ( r = 0.356 , P < 0.05 ) expressions of ANGPTL4 were both closely associated with Pfirrmann grades. The expression of ANGPTL4 was remarkably increased in the groups of high IVDD Pfirrmann grades. Conclusion. The results demonstrated that ANGPTL4 expression was positively associated with the Pfirrmann grades and the severity of intervertebral disc degeneration. ANGPTL4 may be served as a candidate biomarker for intervertebral disc degeneration.

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“…Autophagy is an evolutionarily conserved cellular behavior through which the aberrant organelles and proteins induced by cellular stress can be eliminated ( Mizushima and Komatsu, 2011 ; Wang et al, 2019 ). Previous studies showed that autophagy played a protective role for IDD, and activation of autophagy might be an efficacious treatment ( Ye et al, 2018 ; Kang et al, 2019 ). Recent studies reported that the expression and activation of SIRT1, a NAD + -dependent deacetylase, might play an important protective role in maintaining IVDs homeostasis ( Jiang et al, 2014 ; Wang et al, 2016 ; Zhang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway

Wang

et al. 2020

Front. Cell Dev. Biol.

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Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which causes an enormous socioeconomic burden. Previous studies demonstrated that the apoptosis of nucleus pulposus (NP) cells and the dyshomeostasis of extracellular matrix (ECM) contributed to the pathogenesis of IDD, and effective therapies were still lacking. Quercetin, a natural flavonoid possessing a specific effect of autophagy stimulation and SIRT1 activation, showed some protective effect on a series of degenerative diseases. Based on previous studies, we hypothesized that quercetin might have therapeutic effects on IDD by inhibiting the apoptosis of NP cells and dyshomeostasis of ECM via the SIRT1-autophagy pathway. In this study, we revealed that quercetin treatment inhibited the apoptosis of NP cells and ECM degeneration induced by oxidative stress. We also found that quercetin promoted the expression of SIRT1 and autophagy in NP cells in a dose-dependent manner. Autophagy inhibitor 3-methyladenine (3-MA) reversed the protective effect of quercetin on apoptosis and ECM degeneration. Moreover, SIRT1 enzymatic activity inhibitor EX-527, suppressed quercetin-induced autophagy and the protective effect on NP cells, indicating that quercetin protected NP cells against apoptosis and prevented ECM degeneration via SIRT1-autophagy pathway. In vivo, quercetin was also demonstrated to alleviate the progression of IDD in rats. Taken together, our results suggest that quercetin prevents IDD by promoting SIRT1-dependent autophagy, indicating one novel and effective therapeutic method for IDD.

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Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway

Cited by 11 publications

References 35 publications

CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

CCL2 is a critical mechano‐responsive mediator in crosstalk between osteoblasts and bone mesenchymal stromal cells

Expression of ANGPTL4 in Nucleus Pulposus Tissues Is Associated with Intervertebral Disc Degeneration

Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway

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