Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

Li, Pei; Ye, Gan; Wang, Haoming; Xu, Yuan; Song, Lei; Zhang, Chengmin; Li, Songtao; Zhou, Qiang

doi:10.1159/000446363

Cited by 6 publications

(7 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excessive compressive loading is regarded as a negative external factor for disc biology [ 48 ]. In line with this opinion, our previous study also demonstrated that a high compressive magnitude induced degenerative changes within the disc tissue, such as decreased matrix biochemical content, upregulated matrix degrading enzymes and downregulated matrix genes and tissue inhibitors of matrix metalloproteinase [ 42 , 46 , 49 ]. Together, the attenuated matrix homeostatic phenotype of NP cells under high-magnitude compression also indirectly suggests that high-magnitude compression promotes NP cell senescence.…”

Section: Discussionsupporting

confidence: 67%

“…Eighteen healthy experimental animals (Sprague-Dawley rats, male, 320–340 g, 12 weeks old) were maintained in standard housing and husbandry conditions before starting this study. The lumbar discs (L1–L5) were harvested as described in a previous study [ 42 ]. Then, the discs were cultured for 10 days in the tissue culture chamber of our self-developed bioreactor and compressed at a magnitude of 0.1 or 1.3 MP (1.0 Hz, 6 hours per day).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

Hao

Zhang

et al. 2017

Arthritis Res Ther

Self Cite

View full text Add to dashboard Cite

BackgroundMechanical overloading can lead to disc degeneration. Nucleus pulposus (NP) cell senescence is aggravated within the degenerated disc. This study was designed to investigate the effects of high compression on NP cell senescence and the underlying molecular mechanism of this process.MethodsRat NP cells seeded in decalcified bone matrix were subjected to non-compression (control) or compression (2% or 20% deformation, 1.0 Hz, 6 hours/day). The reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580 were used to investigate the roles of the ROS and p38 MAPK pathway under high-magnitude compression. Additionally, we studied the effects of compression (0.1 or 1.3 MPa, 1.0 Hz, 6 hours/day) in a rat disc organ culture.ResultsBoth in scaffold and organ cultures, high-magnitude compression (20% deformation or 1.3 MPa) increased senescence-associated β-galactosidase (SA-β-Gal) activity, senescence marker (p16 and p53) expression, G1 cell cycle arrest, and ROS generation, and decreased cell proliferation, telomerase activity and matrix (aggrecan and collagen II) synthesis. Further analysis of the 20% deformation group showed that NAC inhibited NP cell senescence but had no obvious effect on phospho-p38 MAPK expression and that SB203580 significantly attenuated ROS generation and NP cell senescence.ConclusionsHigh-magnitude compression can accelerate NP cell senescence through the p38 MAPK-ROS pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1384-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Methodsmentioning

confidence: 99%

High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

Hao

Zhang

et al. 2017

Arthritis Res Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…IDD largely contributes to low back pain [3]. As a mechanical element of the spine, it is subjected to various mechanical stimuli during daily activities [7,19,20]. It has been established that mechanical overload is an important pathological factor to initiate and aggravate disc degeneration [13–15].…”

Section: Discussionmentioning

confidence: 99%

Extensive mechanical tension promotes annulus fibrosus cell senescence through suppressing cellular autophagy

Zhao

Tian

et al. 2019

Bioscience Reports

View full text Add to dashboard Cite

Background: Mechanical load contributes a lot to the initiation and progression of disc degeneration. Annulus fibrosus (AF) cell biology under mechanical tension remains largely unclear. Objective: The present study was aimed to investigate AF cell senescence under mechanical tension and the potential role of autophagy. Methods: Rat AF cells were cultured and experienced different magnitudes (5% elongation and 20% elongation) of mechanical tension for 12 days. Control AF cells were kept static. Cell proliferation, telomerase activity, cell cycle fraction, and expression of senescence-related molecules (p16 and p53) and matrix macromolecules (aggrecan and collagen I) were analyzed to evaluate cell senescence. In addition, expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I were analyzed to investigate cell autophagy. Results: Compared with the control group and 5% tension group, 20% tension group significantly decreased cell proliferation potency and telomerase activity, increased G1/G0 phase fraction, and up-regulated gene/protein expression of p16 and p53, whereas down-regulated gene/protein expression of aggrecan and collagen I. In addition, autophagy-related parameters such as gene/protein expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I, were obviously suppressed in the 20% tension group. Conclusion: High mechanical tension promotes AF cell senescence though suppressing cellular autophagy. The present study will help us to better understand AF cell biology under mechanical tension and mechanical load-related disc degeneration.

show abstract

“…Previous studies and our own investigations have demonstrated that mechanical compression has an important role in regulating disc NP cell biology [18-21]. To investigate effects of mechanical compression on the matrix production of 3D-cultured NP cells, we analyzed for the first time the expression of NP cell-specific markers (keratin-19, FOXF1 and PAX1) under mechanical compression.…”

Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, the disc NP cells are subjected to various kinds of mechanical compression [17], which have a great influence on disc NP cell biology, including cell phenotype and matrix biosynthesis [18-21]. Among the types of mechanical loads, static compression and dynamic compression have usually been applied in the research field of disc degeneration [22-24].…”

Section: Introductionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. Methods: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. Results: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. Conclusion: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

show abstract

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

Cited by 6 publications

References 41 publications

High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway

Extensive mechanical tension promotes annulus fibrosus cell senescence through suppressing cellular autophagy

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Contact Info

Product

Resources

About