Insights into the Hallmarks of Human Nucleus Pulposus Cells with Particular Reference to Cell Viability, Phagocytic Potential and Long Process Formation

Chen, Yufei; Zhang, Yongzhao; Zhang, Weilin; Luan, Guan-Nan; Liu, Zhiheng; Gao, Yang; Wan, Zhong-Yuan; Sun, Zhen; Zhu, Shu; Samartzis, D; Wang, Chunmei; Wang, Hai-Qiang; Luo, Zhuojing

doi:10.7150/ijms.6530

Cited by 17 publications

(17 citation statements)

References 51 publications

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“…NP cells with long processes are found in degenerative and scoliotic NP, which is one of the characteristics of IVD degeneration. 22,23 However, fibroblast-like transformation of NP cells was not observed during the period of cultivation in the current experiment. All NP cells showed a chondrogenic phenotype under both oxygen partial pressures, and cells had similar viability.…”

Section: Discussioncontrasting

confidence: 51%

“…A major concern of the long‐term in vitro expansion period may cause a transformation of chondrocyte‐like NP cells into fibroblast‐like or irregularly shaped cells. NP cells with long processes are found in degenerative and scoliotic NP, which is one of the characteristics of IVD degeneration . However, fibroblast‐like transformation of NP cells was not observed during the period of cultivation in the current experiment.…”

Section: Discussionmentioning

confidence: 51%

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The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Yang

et al. 2017

J Biomedical Materials Res

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Nucleus pulposus (NP) cells locate in the center of avascular intervertebral discs, and thus have presumably adapted to a hypoxic environment. The purpose of this study was to investigate the influences of hypoxic condition, during isolation-expansion of human NP cells, on the cellular proliferation and extracellular matrix (ECM) synthesis in later three-dimensional cultures. Human NP tissues were obtained from patients who underwent lumbar disc surgeries. Immediately after retrieval, NP tissues from each patient were divided into two aliquots for in vitro cultivation either under classical normoxic (21% O ) or hypoxic (3.5% O ) condition. After isolation-expansion processes, microtissues of NP cells were formed and the analysis was performed after one-week culture. Experiments of pretreatment with TGF-β1 or lovastatin were designed to investigate if the isolation-expansion conditions affect the responsiveness to later exogenous treatments. Hypoxic isolation-expansion stimulated NP cell proliferation during monolayer culture. Hypoxia also upregulated mRNA levels of SOX9 and HIF-1α but downregulated type X collagen as well as improved aggrecan and type II collagen synthesis. Although TGF-β1 had no substantial effect, lovastatin pretreatment showed a greater enhancement on type II collagen expression in hypoxic group. Normoxia negatively affected the biochemical composition of regenerated ECM attributable to downregulation of SOX9 and HIF-1α, while hypoxia enhanced cellular proliferation, improved matrix production, and maintained a functional phenotype of NP cells. Hypoxic isolation-expansion of human NP cells is important to achieve better regenerative cells for later cultivation or cell transplantation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1575-1582, 2017.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 51%

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Yang

et al. 2017

J Biomedical Materials Res

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“…Strikingly, lumbar discs are among the early degenerative organs in the body, even in the first decade (Roberts et al 2006). The degeneration sign initiates from cell phenotype conversion from notochord cells to small chondrocyte-like nucleus pulposus cells localized within nests (Chen et al 2013). If we judge lumbar spine discs in terms of more sensitive molecular or RNA expression profiling criteria as we addressed previously (Sun et al 2013; Wan et al 2014; Wang et al 2010, 2011), even early degeneration as phenotype B would be diagnosed as LDD.…”

Section: Discussionmentioning

confidence: 99%

Identification of lumbar disc disease hallmarks: a large cross-sectional study

et al. 2016

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BackgroundLumbar disc disease has a disabling impact on global people with heavy burden on society, mainly consisting of lumbar disc degeneration (LDD) and lumbar disc herniation (LDH). The recently released lumbar disc nomenclature version 2.0 deepens our understandings on the diseases. Consequently, there is an urgent need to clarify the occurrence and distribution features of LDD and LDH in a large-scale sample in terms of the novel version.Question/purposesWe asked: (1) Is there a difference in the occurrence and distribution hallmarks of LDD and LDH in a population-based large-scale sample? (2) Does the novel nomenclature version bring novel vision on lumbar disc disease?MethodsFive thousand two hundred eighty-eight consecutive cases (26,440 lumbar discs) undergoing lumbar spine MRI were retrospectively included from Jan 2008 to Dec 2010 in a territory university hospital. Five hundred nine cases were excluded. There were 2727 males (51.57%) and 2561 females (48.43%) with a mean age of 43.73 years. Both T1 and T2 weighted lumbar MRI images from L1/2 to L5/S1 were profoundly analyzed in axial and sagittal planes. We classified lumbar discs in terms of version 2.0.ResultsThe occurrence of LDH and LDD was 14.18 and 44.23% in average, respectively. Notably, lumbar spine discs were more prone to LDD than LDH. L4/5 was the most frequent level in terms of LDH (26.08%) and LDD (56.09%), followed by L5/S1 (LDH: 24.09%; LDD: 55.33%), then L3/4, L2/3 and L1/2 in ranking order. The prevalence of LDH and LDD in upper lumbar discs from L1/2 to L3/4 was significant lower than the average prevalence rate (P < 0.05). The mean age was 24.70 (±14.81) years for normal lumbar discs; 49.76 (±14.95) years for LDD; 37.01 (±12.91) years for LDH; 51.31(±15.00) years for LDD and LDH (P < 0.05). Modic changes, HIZ, spondylosis deformans and decreased disc height were linked with older age; whereas Schmorl node and lumbar disc sequestration were not associated with age (P < 0.05).ConclusionsThe prevalence of LDD is 44.23%, higher than LDH as 14.18%. L4/5 and L5/S1 are the most frequent involved segments for the majority of lumbar disc diseases. Schmorl node occurs (1.6%) more frequently in upper lumbar spine, independent of age. Modic changes (0.87%) are closely related with older age.Clinical relevanceWhen diagnosing and treating lumbar disc disease, it might be important to consider the updated nomenclature of LDD and LDH. Our study provides additional novel vision on the features of LDD and LDH in a large-scale sample based on the nomenclature of novel version.

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“…The role of apoptosis and apoptosis-related genes in the development of degenerative diseases has garnered much attention in recent years. The excessive apoptosis of NP cells, which are capable of producing ECM components, is one of the most discernable cellular and biochemical changes credited to degeneration (17)(18)(19)(20)(21)(22). A previous study demonstrated that NP cells predominantly undergo apoptosis via the death receptor pathway, which contributes to degeneration of the intervertebral disc (23).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells

Wang

Zhu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Previous studies have demonstrated that the expression levels of cytokines are increased in degenerated intervertebral disc tissues, and several cytokines are associated with the pathogenesis of intervertebral disc degeneration. However, the role of interleukin (IL)-2 in the cellular functions of intervertebral disc tissues remains unreported. The present study aimed to determine the expression levels of IL-2 in the nucleus pulposus (NP) tissues of patients with a prolapsed lumbar intervertebral disc; and to observe the changes in cell proliferation, apoptosis, extracellular matrix (ECM) metabolism and p38 mitogen-activated protein kinase (MAPK) signaling in human NP cells (HNPCs) following treatment with IL-2. The present study demonstrated that IL-2 expression levels were upregulated in the NP tissues of patients with a prolapsed lumbar intervertebral disc; and a subsequent MTT assay demonstrated that IL-2 inhibits the proliferation of HNPCs in a dose-dependent manner. Furthermore, as demonstrated by the increased protein expression levels of Fas cell surface death receptor and the induction of caspase-8 and caspase-3 activity, the death receptor pathway was activated by IL-2 in the HNPCs in order to promote cell apoptosis. In addition, IL-2 promoted ECM degradation in the HNPCs, as demonstrated by an increase in the expression levels of type I collagen, a disintegrin and metalloproteinase with thrombospondin motifs and matrix metalloproteinases, and decreased aggrecan and type II collagen expression levels. Furthermore, phosphorylated-p38 was significantly increased in the HNPCs following IL-2 treatment. In conclusion, the present study demonstrated that IL-2 inhibits cell proliferation, and induces cell apoptosis and ECM degradation, accompanied by the activation of p38 MAPK signaling in HNPCs. Therefore, IL-2 may be a potential therapeutic agent for the treatment of degenerative disc disease. IntroductionThe prolapse of a lumbar intervertebral disc is a common ailment that places pressure on the surrounding nerves and causes pain in the waist and leg. Intervertebral disc degeneration (IDD) has been demonstrated to be the main cause of lumbar intervertebral disc prolapse. Approximately 20% of teenage indiciduals have discs with mild signs of degeneration, while ~10% of 50-year-old individuals and ~60% of 70-year-old individuals posses discs that exhibit severe degeneration (1). However, the pathogenesis of IDD is associated with various cellular and biochemical alterations (2). IDD is associated with numerous risk factors, including lifestyle, co-morbidities, genetic predisposition and age (3).Previous studies have detected high expression levels of cytokines in degenerated intervertebral disc tissues, including interleukin (IL)-1, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and these cytokines are associated with the pathogenesis of IDD (4-6).IL-2, which is a pleiotropic cytokine primarily produced by T lymphocytes, has been implicated in the development and control of inflammatory disea...

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Insights into the Hallmarks of Human Nucleus Pulposus Cells with Particular Reference to Cell Viability, Phagocytic Potential and Long Process Formation

Cited by 17 publications

References 51 publications

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation‐expansion process

Identification of lumbar disc disease hallmarks: a large cross-sectional study

Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells

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