Intervention of rAAV-<i>hTERT</i>-Transducted Nucleus Pulposus Cells in Early Stage of Intervertebral Disc Degeneration: A Study in Canine Model

Shi, Zhiyuan; Gu, Tao; Xin, Hongkui; Wu, Jianhong; Xu, Chen; Zhang, Chao; He, Qiang; Ruan, Dike

doi:10.1089/ten.tea.2014.0408

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…NP is predominantly composed of collagen-II and aggrecan, and the decrease of collagen-II is associated with disc degeneration (23,24). The present study demonstrated that GDF-5 prevented the loss of collagen-II and aggrecan that was induced by LPS.…”

Section: Discussionsupporting

confidence: 60%

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

Shen

Han

et al. 2018

Exp Ther Med

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Abstract. Low back pain (LBP) is one of the most common musculoskeletal diseases in the world. The incidence is ~70% in adults and many of them suffer from disability. Recently, intervertebral disc degeneration (IDD) has been deemed as a main cause of LBP. The present study aimed to investigate the potentials of growth and differentiation factor-5 (GDF-5) in IDD. The protein levels of prostaglandin-E2 (PGE2), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in culture medium were evaluated by ELISA. mRNA and protein expression levels in nucleus pulposus (NP) cells were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Griess reaction was applied to test the nitric oxide (NO) concentration in the culture supernatant. The expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in NP cells were measured by RT-qPCR. Collagen-II, aggrecan, IκBα and phosphorylated (p)-p65 expression levels were detected by western blotting. Compared with the control group, protein expression levels of TNF-α, IL-1β and PGE2, and NO concentration in culture medium were upregulated by LPS, which were significantly repressed by GDF-5 overexpression (P<0.05). Additionally, GDF-5 overexpression reduced lipopolysaccharide-induced upregulation of TNF-α, IL-1β, iNOS, COX-2, collagen-II, aggrecan, IκBα and p-p65 expression levels in NP cells. IntroductionLow back pain (LBP) is one of the most common musculoskeletal diseases in the world, with an incidence of ~70% in adults (1). Unfortunately, many of those with LBP suffer from disability (1). Multiple causes could lead to LBP; however, intervertebral disc degeneration (IDD) and disc herniation are reported to be the two most common diagnoses and targets for intervention (2), with IDD being deemed as the main cause of LBP (3,4). IDD is a multifactorial process that is characterized by cellular and biochemical changes in the disc tissue, consequently generating structural failure (5).A normal disc is composed of two types of tissues, the nucleus pulposus (NP) and the annulus fibrosus (AF), and they serve different roles in load bearing. Gelatinous NP is predominantly composed of type II collagen and proteoglycans, and its relatively higher water content (compared to AF tissues) is responsible for its resistance to compressive forces and hydrostatic pressurization (6,7). In degeneration, loss of proteoglycans and water signal intensity is detected by changes in disc height and T2-weighted magnetic resonance imaging (MRI) signal in the NP (8), which may lead to redistribution of load onto fibrochondrocyte-like cells in the AF (9).As IDD is associated with normal aging, many people with IDD indications on MRI do not suffer with pain or disability (10,11). However, current treatments for IDD, including surgery, steroid injection and physical therapy, treat symptoms and not disc structure/function regeneration.Inflammation is correlated with IDD and it involves various cells and molecules (12). Multiple g...

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Section: Discussionsupporting

confidence: 60%

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

Shen

Han

et al. 2018

Exp Ther Med

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“…Inhibitors of MMPs and ADAMTSs have a therapeutic effect on OA ( Gilbert et al, 2007 ) and IDD ( Leckie et al, 2012 ) in vitro and in vivo . Collagen-II and aggrecan are the main components of nucleus pulposus, and the reduction of collagen-II content is highly correlated with disc degeneration ( Shi et al, 2015 ; Kozaci et al, 2006 ). Our study shows that cordycepin can both prevent LPS-induced collagen-II and aggrecan loss and promote their synthesis.…”

Section: Discussionmentioning

confidence: 99%

Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc

Mao

et al. 2016

PeerJ

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Cordycepin is a component of the extract obtained from Cordyceps militaris and has many biological activities, including anti-cancer, anti-metastatic and anti-inflammatory effects. Intervertebral disc degeneration (IDD) is a degenerative disease that is closely related to the inflammation of nucleus pulposus (NP) cells. The effect of cordycepin on NP cells in relation to inflammation and degeneration has not yet been studied. In our study, we used a rat NP cell culture and an intervertebral disc (IVD) organ culture model to examine the inhibitory effects of cordycepin on lipopolysaccharide (LPS)-induced gene expression and the production of matrix degradation enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5) and oxidative stress-associated factors (nitric oxide and PGE2). We found a protective effect of cordycepin on NP cells and IVDs against LPS-induced matrix degradation and macrophage infiltration. In addition, western blot and luciferase assay results demonstrated that pretreatment with cordycepin significantly suppressed the LPS-induced activation of the NF-κB pathway. Taken together, the results of our research suggest that cordycepin could exert anti-inflammatory and anti-degenerative effects on NP cells and IVDs by inhibiting the activation of the NF-κB pathway. Therefore, cordycepin may be a potential treatment for IDD in the future.

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“…It showed an increase in Col II (73 pg/mg) than Col I (61 pg/mg) in different lumbar segments of group A (L1, L2) and much higher Col I content (266 pg/mg) in group B (L3, L4) than other groups compared with group C (L5, L6) and A (L1, L2). Therefore, (RAAV)-(hTERT)-(NPCs) increased the ECM content and helped in delaying the degeneration process in the canine model . It has also been shown to restore basic IVD function to evade difficulties generated by decompressive procedures and stabilization.…”

Section: Methods Of Developing In Vivo Ivd Injury Modelmentioning

confidence: 99%

“…Therefore, (RAAV)-(hTERT)-(NPCs) increased the ECM content and helped in delaying the degeneration process in the canine model. 85 It has also been shown to restore basic IVD function to evade difficulties generated by decompressive procedures and stabilization. A novel nucleus pulposus prosthesis (NPP) exhibits a range of motion (ROM), neutral zone (NZ), and neutral zone stiffness (NZS) when subjected to cycling loading, NZS restored the functionality, and could enhance the functionality of IVDD.…”

Section: Modelmentioning

confidence: 99%

Evaluation of Tissue Engineering Approaches for Intervertebral Disc Regeneration in Relevant Animal Models

Malli

Kumbhkarn

Dewle

et al. 2021

ACS Appl. Bio Mater.

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Translation of tissue engineering strategies for the regeneration of intervertebral disc (IVD) requires a strong understanding of pathophysiology through the relevant animal model. There is no relevant animal model due to differences in disc anatomy, cellular composition, extracellular matrix components, disc physiology, and mechanical strength from humans. However, available animal models if used correctly could provide clinically relevant information for the translation into humans. In this review, we have investigated different types of strategies for the development of clinically relevant animal models to study biomaterials, cells, biomolecular or their combination in developing tissue engineering-based treatment strategies. Tissue engineering strategies that utilize various animal models for IVD regeneration are summarized and outcomes have been discussed. The understanding of animal models for the validation of regenerative approaches is employed to understand and treat the pathophysiology of degenerative disc disease (DDD) before proceeding for human trials. These animal models play an important role in building a therapeutic regime for IVD tissue regeneration, which can serve as a platform for clinical applications.

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Intervention of rAAV-hTERT-Transducted Nucleus Pulposus Cells in Early Stage of Intervertebral Disc Degeneration: A Study in Canine Model

Abstract: In 12 weeks of observation, rAAV-hTERT-transducted NPCs could delay the degeneration process in the canine model which was superior than the capacity of NPCs in preserving structure integrity, content of extracellular matrix, and mechanical stability.

Cited by 7 publications

References 34 publications

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

Cordycepin inhibits LPS-induced inflammatory and matrix degradation in the intervertebral disc

Evaluation of Tissue Engineering Approaches for Intervertebral Disc Regeneration in Relevant Animal Models

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