Accumulated Spinal Axial Biomechanical Loading Induces Degeneration in Intervertebral Disc of Mice Lumbar Spine

Lao, Yangjun; Xu, Tao‐tao; Jin, Hongting; Ruan, Hongfeng; Wang, Ji‐tao; Zhou, Li; Wang, Pinger; Wang, Jian; Ying, Jun; Zhang, Yuan‐bin; Luo, Cheng; Fu, Fangda; Tong, Pei-Jian; Liang, Xiao; Wu, Chengliang

doi:10.1111/os.12365

Cited by 7 publications

(6 citation statements)

References 19 publications

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“…In some experiments on mice that have led to disc degeneration, abnormal expression of type X collagen, increased apoptosis, inappropriate intervertebral disc ossification, and elevated expression of COL10A1, Runx2, MMP-13, etc. were observed in degenerative NP [ 11 , 49 – 51 ]. Our network analysis also has confirmed that COL10A plays an important role in the pathogenesis of IDD.…”

Section: Discussionmentioning

confidence: 99%

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

Huang

et al. 2021

BioMed Research International

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Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA–miRNA–mRNA interaction network was constructed. NEAT1–miR-5100–COL10A1 and miR663AHG/HEIH/hsa-circ-0003600–miR-4741–HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD.

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Section: Discussionmentioning

confidence: 99%

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

Huang

et al. 2021

BioMed Research International

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“…When the spine is under abnormal loading, the proteoglycan content in the VEP will change, promoting its calcification and reducing its elasticity, in addition to weakening the abilities of the spine to absorb shock and evenly transmit weight [42]. Furthermore, the accumulation of metabolites in the IVD can activate catabolic enzymes, causing matrix destruction, cellular metabolic disorders, and cell death [43,44]. Relevant studies [11][12][13] have also confirmed that an abnormal load can slow the blood flow inside the bony endplate and lead to blood stasis, thereby causing injury to vascular endothelial cells and thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Constant compression decreases vascular bud and VEGFA expression in a rabbit vertebral endplate ex vivo culture model

et al. 2020

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of background data The vascular buds in the vertebral endplate (VEP) are the structural foundation of nutrient exchange in the intervertebral disc (IVD). VEGF is closely related to angiogenesis in the endplate and intervertebral disc degeneration (IDD). Objective To investigate the effects of static load on vascular buds and VEGF expression in the VEP and to further clarify the relation between IDD and VEGF. Methods IVD motion segments were harvested from rabbit lumbar spines and cultured under no-loading conditions (controls) or in custom-made apparatuses under a constant compressive load (0.5 MPa) for up to 14 days. Tissue integrity and the number of vascular buds were determined, and the concentrations and expression of Aggrecan, COL2a1, and VEGFA in the VEPs were assessed after 3, 7, and 14 days of culturing and then compared with those of fresh tissues. Results Under the constant compression, the morphological integrity of the VEPs was gradually disrupted, and immunohistochemistry results showed a significant decrease in the levels of Agg and COL2a1. During the static load, the number of vascular buds in the VEPs was gradually reduced from the early stage of culture, and ELISA showed that the constant compressive load caused a significant decrease in the VEGFA and VEGFR2 protein concentrations, which were consistent with the immunohistochemistry results. Western blot and RT-PCR

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“…As such, a wide array of mechanically induced models have been developed that alter or modify the mechanical environment experienced by mice IVDs to induce degeneration. Instability models such as surgical resection of posterior elements (i.e., facet joints and spinous processes), tail bending, static/dynamic compression, and axial loading models have demonstrated that altering the mechanical loading environment applied to the IVD can lead to progressive disc degeneration characterized by cell death, decreased disc height, decreased collagen II and aggrecan expression, and disorganization of AF structure (67)(68)(69)(70)(71)(72)(73)(74). Other models which alter spinal loading via induced bipedal behaviors exhibit accelerated degenerative characteristics due to abnormal mechanical stress compared to quadrupedal mice (75,76).…”

Section: Mechanically Induced and Puncture Modelsmentioning

confidence: 99%

In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review

et al. 2022

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Low back pain is a leading cause of disability worldwide and studies have demonstrated intervertebral disc (IVD) degeneration as a major risk factor. While many in vitro models have been developed and used to study IVD pathophysiology and therapeutic strategies, the etiology of IVD degeneration is a complex multifactorial process involving crosstalk of nearby tissues and systemic effects. Thus, the use of appropriate in vivo models is necessary to fully understand the associated molecular, structural, and functional changes and how they relate to pain. Mouse models have been widely adopted due to accessibility and ease of genetic manipulation compared to other animal models. Despite their small size, mice lumbar discs demonstrate significant similarities to the human IVD in terms of geometry, structure, and mechanical properties. While several different mouse models of IVD degeneration exist, greater standardization of the methods for inducing degeneration and the development of a consistent set of output measurements could allow mouse models to become a stronger tool for clinical translation. This article reviews current mouse models of IVD degeneration in the context of clinical translation and highlights a critical set of output measurements for studying disease pathology or screening regenerative therapies with an emphasis on pain phenotyping. First, we summarized and categorized these models into genetic, age-related, and mechanically induced. Then, the outcome parameters assessed in these models are compared including, molecular, cellular, functional/structural, and pain assessments for both evoked and spontaneous pain. These comparisons highlight a set of potential key parameters that can be used to validate the model and inform its utility to screen potential therapies for IVD degeneration and their translation to the human condition. As treatment of symptomatic pain is important, this review provides an emphasis on critical pain-like behavior assessments in mice and explores current behavioral assessments relevant to discogenic back pain. Overall, the specific research question was determined to be essential to identify the relevant model with histological staining, imaging, extracellular matrix composition, mechanics, and pain as critical parameters for assessing degeneration and regenerative strategies.

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Accumulated Spinal Axial Biomechanical Loading Induces Degeneration in Intervertebral Disc of Mice Lumbar Spine

Abstract: Accumulated spinal axial loading provided by a custom-made hot plate accelerated mice lumbar disc and especially endplate degeneration. However, this method requires further development to establish a lumbar disc degeneration model.

Cited by 7 publications

References 19 publications

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

Constant compression decreases vascular bud and VEGFA expression in a rabbit vertebral endplate ex vivo culture model

In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review

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