Advancing the cellular and molecular therapy for intervertebral disc disease

Sakai, Daisuke; Grad, Sibylle

doi:10.1016/j.addr.2014.06.009

Cited by 253 publications

(230 citation statements)

References 182 publications

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“…Although disc cell death through apoptosis is closely associated with development of IVDD, the underlying mechanisms are not fully elucidated. Under hypoxic conditions, disc cell metabolism is partially anaerobic, resulting in high concentrations of lactic acid and an acidic environment that is enhanced by the presence of cytokines [62,63]. Matrix acidity has a potentially negative effect on gene expression, proliferation and viability of disc cells [64].…”

Section: Asics and Intervertebral Disc Degenerationmentioning

confidence: 99%

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Zhou

Wang³

et al. 2016

Aging and disease

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Section: Asics and Intervertebral Disc Degenerationmentioning

confidence: 99%

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Zhou

Wang³

et al. 2016

Aging and disease

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“…cell-or growth factor-based regenerative strategies have gained increased attention (Bach et al, 2014;Benneker et al, 2014;Sakai and Grad, 2015;Sakai and Andersson, 2015). Although several regenerative strategies, e.g.…”

Section: Identification Of the Bioactive Factors In Nccmmentioning

confidence: 99%

Soluble and pelletable factors in porcine, canine and human notochordal cell-conditioned medium: implications for IVD regeneration

Bach

Vries

Riemers³

et al. 2016

eCM

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During intervertebral disc (IVD) maturation, notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) in the nucleus pulposus, suggesting that NCs play a role in maintaining tissue health. Affirmatively, NC-conditioned medium (NCCM) exerts regenerative effects on CLC proliferation and extracellular matrix (ECM) production. The aim of this study was to identify NC-secreted substances that stimulate IVD regeneration. By mass spectrometry of porcine, canine and human NCCM, 149, 170 and 217 proteins were identified, respectively, with 66 proteins in common. Mainly ECM-related proteins were identified, but also organelle-derived and membranebound vesicle proteins. To determine whether the effect of NCCM was mediated by soluble and/or pelletable factors, porcine and canine NCCM were separated into a soluble (NCCM-S; peptides and proteins) and pelletable (NCCM-P; protein aggregates and extracellular vesicles) fraction by ultracentrifugation, and tested on bovine and canine CLCs in vitro, respectively. In each model, NCCM-S exerted a more pronounced anabolic effect than NCCM-P. However, glycosaminoglycan (GAG) uptake from the medium into the carrier gel prevented more definite conclusions. While the effect of porcine NCCM-P on bovine CLCs was negligible, canine NCCM-P appeared to enhance GAG and collagen type II deposition by canine CLCs. In conclusion, porcine and canine NCCM exerted their anabolic effects mainly through soluble factors, but also the pelletable NCCM factors showed moderate regenerative potential. Although the regenerative potential of NCCM-P should not be overlooked, future studies should focus on unraveling the protein-based regenerative mechanism from NCCM produced from isolated NCs, e.g. by NCCM fractionation and pathway blocking studies.

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“…Precisely because of the high NP hydration resulted from the negatively charged glycosaminoglycan, the disc allows for spine motion and maintains a uniform stress distribution of the disc endplates. However, the disc NP region undergoes progressive biochemical changes during degeneration and aging, such as decrease in proteoglycan content, decline of tissue hydration and transition of collagen type I to collagen type II [37], which can return signi icantly broken disc mechanical function. Therefore, strategies that can restore matrix homeostasis within the disc NP region may be feasible to partly regenerate the degenerated disc.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

Li¹,

Xu²,

Ye³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP) tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E₂) in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10^-5, 10^-7 and 10^-9 M) or without (control) E2 for48 hours. The estrogen receptor (ER)-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG) content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

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Advancing the cellular and molecular therapy for intervertebral disc disease

Cited by 253 publications

References 182 publications

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Soluble and pelletable factors in porcine, canine and human notochordal cell-conditioned medium: implications for IVD regeneration

Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

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