scholarly journals Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Yiyang Wang ◽  
Baoshuai Bai ◽  
Yanzhu Hu ◽  
Haoming Wang ◽  
Ningyuan Liu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hydrostatic Pressure ◽  
Intervertebral Disc ◽  
Cell Survival ◽  
Biological Behavior ◽  
The Difference ◽  
Matrix Metabolism ◽  
Ivd Degeneration ◽  
Loading Devices

Established studies proved that hydrostatic pressure had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the conclusions of the previous studies were inconsistent, due to the difference in hydrostatic loading devices and observing methods used in these studies. The current study is aimed at investigating the role of dynamic hydrostatic pressure in regulating biological behavior of the notochordal nucleus pulposus (NP) and fibrocartilaginous inner annulus fibrosus (AF) and its possible mechanism using our novel self-developed hydrostatic pressure bioreactor. The differences in the biological behavior of the rabbit IVD tissues under different degree of hydrostatic pressure were evaluated via histological analysis. Results revealed that low-loading dynamic hydrostatic pressure was beneficial for cell survival and extracellular matrix (ECM) homeostasis in notochordal NP and fibrocartilaginous inner AF via upregulating N-cadherin (N-CDH) and integrin β1. In comparison, high-magnitude dynamic hydrostatic pressure aggravated the breakdown of ECM homeostasis in NP and inner AF via enhancing the Hippo-YAP/TAZ pathway-mediated cell apoptosis. Moreover, inner AF exhibited greater tolerance to physiological medium-loading degree of hydrostatic pressure than notochordal NP. The potential mechanism was related to the differential expression of mechanosensing factors in notochordal NP and fibrocartilaginous inner AF, which affects the fate of the cells under hydrostatic pressure. Our findings may provide a better understanding of the regulatory role of hydrostatic pressure on the cellular fate commitment and matrix metabolism of the IVD and more substantial evidence for using hydrostatic pressure bioreactor in exploring the IVD degeneration mechanism as well as regeneration strategies.

scholarly journals The Role Of Extracellular Matrix Elasticity and Composition In Regulating the Nucleus Pulposus Cell Phenotype in the Intervertebral Disc: A Narrative Review

2014 ◽  
Vol 136 (2) ◽  
Author(s):  
Priscilla Y. Hwang ◽  
Jun Chen ◽  
Liufang Jing ◽  
Brenton D. Hoffman ◽  
Lori A. Setton
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Cell Phenotype ◽  
Recent Experience ◽  
Delivery Strategies ◽  
Ivd Degeneration ◽  
Care Costs

Intervertebral disc (IVD) disorders are a major contributor to disability and societal health care costs. Nucleus pulposus (NP) cells of the IVD exhibit changes in both phenotype and morphology with aging-related IVD degeneration that may impact the onset and progression of IVD pathology. Studies have demonstrated that immature NP cell interactions with their extracellular matrix (ECM) may be key regulators of cellular phenotype, metabolism and morphology. The objective of this article is to review our recent experience with studies of NP cell-ECM interactions that reveal how ECM cues can be manipulated to promote an immature NP cell phenotype and morphology. Findings demonstrate the importance of a soft (<700 Pa), laminin-containing ECM in regulating healthy, immature NP cells. Knowledge of NP cell-ECM interactions can be used for development of tissue engineering or cell delivery strategies to treat IVD-related disorders.

Whole-body Vibration Attenuates Pyroptosis-Mediated Inflammation but Accelerates Progression of Intervertebral Disc Degeneration

2020 ◽  
Author(s):  
Fang-da Fu ◽  
Sai Yao ◽  
Zhi-tao Sun ◽  
Cheng-cong Zhou ◽  
Huan Yu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Whole Body Vibration ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Whole Body ◽  
Body Vibration ◽  
Pharmaceutical Therapy ◽  
The Matrix ◽  
Matrix Metabolism ◽  
Ivd Degeneration

Abstract Background Whole body vibration (WBV) is a non-pharmaceutical therapy that has been widely incorporated into clinical practice for musculoskeletal disorders, including low back pain (LBP). Intervertebral disc (IVD) degeneration (IVDD) is clinically associated with LBP and is known as the main cause for LBP. However, cumulative evidence also suggested WBV might have an adverse impact on IVDs. Moreover, previous studies have been focusing on the effects of WBV on healthy mice, rather than those suffering from IVDD. Thus, uncertainties still exist concerning the effects of WBV on IVDs undergoing IVDD. This study was aiming to evaluate the effects of WBV intervention on the development and progression of IVDD mouse model induced by lumbar spine instability (LSI) surgery. Methods LSI surgery, by resecting the lumbar 3 rd -5 th spinous processes along with the supraspinous and interspinous ligaments, was conducted in 10-week-old male mice which then received WBV treatment (1 h per day, 5 days per week, at 3 Hz with peak acceleration at 0.4 g) or sham treatment. The progression of IVDD was evaluated by MRI, μCT and histological analyses after WBV treatment. The matrix metabolism, distribution of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological analysis or real-time PCR. The apoptosis of IVD cells was detected by TUNEL assay. Results LSI surgery was successful in producing IVDD modeling. WBV caused decreases in IVD height and annulus fibrosus (AF) score, as well as increased numbers of apoptotic cells in IVD tissues. WBV contributed to sensory innervation into AF and upregulation of Adamts5 and MMP3 expression in IVDD mice received LSI surgery. In addition, WBV treatment triggered earlier activation of Wnt/β-catenin signaling in IVDD mice with WBV treatment compared with those without WBV treatment. Unexpectedly, WBV significantly attenuated Caspase-1 and IL-1β expression in AF. Conclusions Collectively, our findings demonstrate that WBV treatment may worsen the development of ongoing IVDD. Decrease of IL-1β expression after WBV intervention may partially account for patient self-reported pain relief after WBV treatment in some previous trials. This study may help us better understand the effects of WBV intervention on patients experiencing LBP resulting from the degeneration of lumbar IVDs.

scholarly journals The effects of different hydrostaticpressures on gene expression in vertebral cartilage endplate cells

2020 ◽  
Author(s):  
Qi Sun ◽  
Gen-Zhe Liu ◽  
Jiang Chen ◽  
Yong-Gang Zhu
Keyword(s):  
Gene Expression ◽  
Hydrostatic Pressure ◽  
Pressure System ◽  
Cartilage Endplate ◽  
Cartilage Cells ◽  
Polymerase Chain ◽  
Matrix Metabolism ◽  
Ivd Degeneration ◽  
Metabolism Gene

Abstract Background : The nutrients of the intervertebral disc are mainly provided through penetration from the cartilage endplate, and the stable functional status of the cartilage cells directly influences the function of the cartilage endplate. However, there is no study on gene expression in endplate cells under varying pressure conditions. Knowledge of anabolic/catabolic metabolic alterations of cartilage endplate cells in response to various magnitudes and durations of compression is important to alleviate IVD degeneration through maintenance of extracellular matrix homeostasis and the repair of endplate cartilage. The purpose of this study was to examine the effects of compression on gene expression in vertebral cartilage endplate cells in vitro through a hydrostatic pressure system. Methods : Rabbit vertebral cartilage endplate cells were exposed to hydrostatic pressure at 0.1, 0.7, 2 and 4 MPa for 4 or 24 hours. Real-time polymerase chain reaction was performed to analyze the gene expression of inflammation (iNOS, COX-2), matrix metabolism (MMP-3), anticatabolic metabolism (TIMP-1), and anabolic metabolism (aggrecan). Results : Decreased magnitude and duration showed more anticatabolic/anabolic metabolism gene expression, whereas increased duration resulted in increased catabolic gene expression. Conclusions : Low magnitude or short duration of compression demonstrated more anabolic and anticatabolic gene expression, while increased magnitude and duration showed more procatabolic gene expression.

scholarly journals Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice

Bone Research ◽  
2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Zuqiang Wang ◽  
Hangang Chen ◽  
Qiaoyan Tan ◽  
Junlan Huang ◽  
Siru Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Genetic Ablation ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Current Therapies ◽  
Cartilaginous Endplate ◽  
Ivd Degeneration ◽  
Deficient Mice

AbstractThe intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate (EP) and annulus fibrosus (AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol (2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

scholarly journals Deficiency of MIF Accentuates Overloaded Compression-Induced Nucleus Pulposus Cell Oxidative Damage via Depressing Mitophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yiyang Wang ◽  
Yanzhu Hu ◽  
Haoming Wang ◽  
Ningyuan Liu ◽  
Lei Luo ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Nucleus Pulposus Cell ◽  
Biological Behavior ◽  
Signal Pathways ◽  
Mechanical Compression ◽  
Compression Loading ◽  
Cartilage Endplate ◽  
Tandem Mass Tag ◽  
Matrix Metabolism

Established studies proved that mechanical compression loading had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the regulating mechanism involved in this process remains unclear. The current study is aimed at exploring the potential bioregulators and signaling pathways involved in the compression-associated biological changes of nucleus pulposus (NP) cells. Tandem mass tag- (TMT-) based quantitative proteomics was exerted to analyze the differentially expressed proteins (DEPs) and signal pathways among the different groups of NP cells cultured under noncompression, low-compression (LC), and high-compression (HC) loading. Eight potential protective bioregulators for the NP cell survival under different compression loading were predicted by the proteomics, among which macrophage migration inhibitory factor (MIF) and oxidative stress-related pathways were selected for further evaluation, due to its similar function in regulating the fate of the cartilage endplate- (CEP-) derived cells. We found that deficiency of MIF accentuates the accumulation of ROS, mitochondrial dysfunction, and senescence of NP cells under overloaded mechanical compression. The potential molecular mechanism involved in this process is related to the mitophagy regulating role of MIF. Our findings provide a better understanding of the regulatory role of mechanical compression on the cellular fate commitment and matrix metabolism of NP, and the potential strategies for treating disc degenerative diseases via using MIF-regulating agents.

Ablation of MMP9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics: a role of extracellular matrix

2012 ◽  
Vol 90 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Paras Kumar Mishra ◽  
Vishalakshi Chavali ◽  
Naira Metreveli ◽  
Suresh C. Tyagi
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Confocal Microscopy ◽  
Cell Survival ◽  
Troponin I ◽  
Gelatin Zymography ◽  
Cardiac Stem Cells ◽  
Stem Cell Survival

The contribution of extracellular matrix (ECM) to stem cell survival and differentiation is unequivocal, and matrix metalloproteinase-9 (MMP9) induces ECM turn over; however, the role of MMP9 in the survival and differentiation of cardiac stem cells is unclear. We hypothesize that ablation of MMP9 enhances the survival and differentiation of cardiac stem cells into cardiomyocytes in diabetics. To test our hypothesis, Ins2+/− Akita, C57 BL/6J, and double knock out (DKO: Ins2+/−/MMP9−/−) mice were used. We created the DKO mice by deleting the MMP9 gene from Ins2+/−. The above 3 groups of mice were genotyped. The activity and expression of MMP9 in the 3 groups were determined by in-gel gelatin zymography, Western blotting, and confocal microscopy. To determine the role of MMP9 in ECM stiffness (fibrosis), we measured collagen deposition in the histological sections of hearts using Masson’s trichrome staining. The role of MMP9 in cardiac stem cell survival and differentiation was determined by co-immunoprecipitation (co-IP) of MMP9 with c-kit (a marker of stem cells) and measuring the level of troponin I (a marker of cardiomyocytes) by confocal microscopy in the 3 groups. Our results revealed that ablation of MMP9 (i) reduces the stiffness of ECM by decreasing collagen accumulation (fibrosis), and (ii) enhances the survival (elevated c-kit level) and differentiation of cardiac stem cells into cardiomyocytes (increased troponin I) in diabetes. We conclude that inhibition of MMP9 ameliorates stem cell survival and their differentiation into cardiomyocytes in diabetes.

scholarly journals Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Umile Giuseppe Longo ◽  
Nicola Papapietro ◽  
Stefano Petrillo ◽  
Edoardo Franceschetti ◽  
Nicola Maffulli ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Surgical Intervention ◽  
Pathological Condition ◽  
Treatment Strategies ◽  
Clinical Applications ◽  
Ivd Degeneration

Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.

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