Cellular mechanobiology of the intervertebral disc: New directions and approaches

Hsieh, Adam H.; Twomey, Julianne D.

doi:10.1016/j.jbiomech.2009.09.019

Cited by 87 publications

(77 citation statements)

References 134 publications

(154 reference statements)

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“…In this study, high-magnitude (20% deformation) compression significantly down-regulated N-CDH expression compared with low-magnitude (2% deformation) compression. In light of the reported destructive effects of mechanical overloading on disc NP biology [9, 11, 29, 31], we deduce that N-CDH down-regulation may participate in this process.…”

Section: Discussionmentioning

confidence: 81%

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

Wang

Leng²,

Zhao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mechanical load can regulate disc nucleus pulposus (NP) biology in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N-CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under high-magnitude compression. Methods: Rat NP cells seeded on scaffolds were perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype was studied after the cells were subjected to different compressive magnitudes (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression was used to further investigate the role of N-CDH under high-magnitude compression. Results: The 20% deformation compression condition significantly decreased N-CDH expression compared with the 2% deformation compression and control conditions. Meanwhile, 20% deformation compression increased the number of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3 and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with 2% deformation compression. Additionally, N-CDH overexpression attenuated the effects of 20% deformation compression on NP cell biology in relation to the designated parameters. Conclusion: N-CDH helps to restore the cell viability, matrix biosynthesis and cellular phenotype of NP cells under high-magnitude compression.

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Section: Discussionmentioning

confidence: 81%

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

Wang

Leng²,

Zhao³

et al. 2017

Cell Physiol Biochem

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“…Maintenance of a normal NP cell phenotype is important for synthesizing and secreting a native tissue extracellular matrix. Collagen and proteoglycan are the main macromolecules within the NP matrix [41]. Here, dynamic compression also promoted the gene and protein expression of the NP matrix molecules (aggrecan and collagen II) compared with the expression levels in the cells under static compression, indicating that dynamic compression is helpful to promote the matrix biosynthesis of NP cells compared with the ability of static compression to do so.…”

Section: Discussionmentioning

confidence: 99%

“…Degenerative discs often have a limited number of viable cells, which directly contributes to the decrease in normal disc NP matrix components and results in attenuated disc function [41]. During the past decades, various kinds of cell sources were adopted in constructing cell-based scaffolds to regenerate degenerative discs, such as autologous or xenogenous NP cells and mesenchymal stem cells (MSCs) [42, 43].…”

Section: Discussionmentioning

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

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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.

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“…21,30 The structure of NP is unique within the intervertebral disc, which is under tremendous forces and compressive load environment. 31,32 The exact mechanisms of this effect are complicated, including decreased proteoglycan production, increased apoptosis, the accumulation of inflammatory agents and cell volume changes. [33][34][35] In this study, we found that compressive load is a vital factor to mediate the phosphorylation of CK8 in human NP cells.…”

Section: Discussionmentioning

confidence: 99%

CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C

Sun

Guo

Yan

et al. 2013

Laboratory Investigation

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Cytokeratin 8 (CK8) is a member of the cytokeratins family with multiple functions on the basis of its unique structural hallmark. The aberrant expression of CK8 and its phosphorylation are pertinent with various diseases. We have previously shown that CK8 exists in normal human nucleus pulposus (NP) cells and decreases as the intervertebral disc degenerates. However, the underlying molecular regulatory machinery of CK8 in intervertebral disc degeneration (IDD) has not been clarified. Here, we collected NP samples from patients with idiopathic scoliosis as control and IDD as degenerate groups. We found that CK8 expression decreased in IDD with an increased phosphorylation in degenerate NP cells. Moreover, NP cells were cultured under different compressive load schemes for diverse time duration. We found that compressive loads resulted in phosphorylation and disassembly of CK8 in a time-dependent and degree-dependent manner in vitro. The activation of protein kinase C was a significant molecular factor contributing to this phenomenon. Taken together, this study is the first to address the molecular mechanisms of CK8 downregulation in NP cells. Importantly, our findings provide clues regarding a molecular link between compressive loads and CK8 alterations, which shed a novel light on the etiology of IDD.

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Cellular mechanobiology of the intervertebral disc: New directions and approaches

Cited by 87 publications

References 134 publications

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High-Magnitude Compression

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

CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C

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