Static Compression Induces ECM Remodeling and Integrin α2β1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model

Yan, ZhanJun; Pan, Ying; Wang, ShiHui; Cheng, Mao-Hua; Kong, HongMei; Sun, ChunGuang; Kai, Hu; Chen, TongLei; Dong, Qirong; Chen, Jianfeng

doi:10.1097/brs.0000000000001856

Cited by 48 publications

(34 citation statements)

References 52 publications

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“…Although one study found that physiological level of dynamic compression induced integrin α5β1 expression in rat disc explants 187 , other studies find that degenerative static compressive loading in vivo upregulate β1 expression in NP cells, and activates downstream signaling 188 .…”

Section: Cell-ecm Interactionsmentioning

confidence: 98%

“…Although one study found that physiological level of dynamic compression induced integrin α5β1 expression in rat disc explants, other studies find that degenerative static compressive loading in vivo upregulate β1 expression in NP cells, and activates downstream signaling. Moreover, disruption of β1 integrin signaling may underlie disc cell apoptosis induced by mechanical stress in disc degeneration models.…”

Section: Response To Abnormal Mechanobiology and Degenerationmentioning

confidence: 99%

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Mechanotransduction and cell biomechanics of the intervertebral disc

et al. 2018

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Mechanical loading of the intervertebral disc (IVD) initiates cell-mediated remodeling events that contribute to disc degeneration. Cells of the IVD, nucleus pulposus (NP) and anulus fibrosus (AF), will exhibit various responses to different mechanical stimuli which appear to be highly dependent on loading type, magnitude, duration, and anatomic zone of cell origin. Cells of the NP, the innermost region of the disc, exhibit an anabolic response to low-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure, while higher magnitudes promote a catabolic response marked by increased protease expression and activity. Cells of the outer AF are responsive to physical forces in a manner that depends on frequency and magnitude, as are cells of the NP, though they experience different forces, deformations, pressure, and osmotic pressure in vivo. Much remains to be understood of the mechanotransduction pathways that regulate IVD cell responses to loading, including responses to specific stimuli and also differences among cell types. There is evidence that cytoskeletal remodeling and receptor-mediated signaling are important mechanotransduction events that can regulate downstream effects like gene expression and posttranslational biosynthesis, all of which may influence phenotype and bioactivity. These and other mechanotransduction events will be regulated by known and to-be-discovered cell-matrix and cell-cell interactions, and depend on composition of extracellular matrix ligands for cell interaction, matrix stiffness, and the phenotype of the cells themselves. Here, we present a review of the current knowledge of the role of mechanical stimuli and the impact upon the cellular response to loading and changes that occur with aging and degeneration of the IVD.

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Section: Cell-ecm Interactionsmentioning

confidence: 98%

Section: Response To Abnormal Mechanobiology and Degenerationmentioning

confidence: 99%

Mechanotransduction and cell biomechanics of the intervertebral disc

et al. 2018

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“…Previous studies found an increase in NP cell apoptosis and a decrease in NP matrix production as a result of overloaded mechanical compression [9, 10]. Similarly, several studies have demonstrated that mechanical stimulation plays an important role in regulating disc biology and have indicated that mechanical overloading is a risk factor for disc degeneration [11, 12]. Therefore, additional studies of the high-magnitude compression-induced pathological alterations of NP cells will contribute to a better understanding of mechanical load-related disc degeneration.…”

Section: Introductionmentioning

confidence: 99%

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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“…Further, the degree of degeneration heavily depends on time and the extent of bending force applied to the rat tail. Another classic model, Ilizarov-type compressive model, was widely used by many researchers due to its reliable installation and satisfactory modeling results [11,[22][23][24]. However, a set of springs were mainly used in these studies as the provider of compression loads.…”

Section: Discussionmentioning

confidence: 99%

The Establishment of Intervertebral Endplate Degeneration: A Novel in-vivo Diurnal-Axial Controllable Loading Model in Rat Tail

Hu¹,

He²,

Li³

et al. 2020

Preprint

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Background. Cartilage endplate (CEP) acts as an important mechanical barrier and nutrient channel for the intervertebral disc (IVD). Its vulnerability to excessive loading and subsequent degeneration might be an initial trigger for IVD degeneration. This study aims to build a new in-vivo animal model of rat-tail CEP degeneration through implementing a controllable axial compressive device.Methods. An axial controllable compressive load was conducted on the 8–9 th coccygeal IVD of adult rat tail through puncturing 4 Kirschner wires into its superior and inferior vertebra. The exact compression loads were controlled and adjusted by a remote controller. The compression and decompression periods were set as 8 h/16 h per day. The control group was set as no device installation, while the Kirschner wires were punctured without compression in the sham group. After each 4, 8 and 12 weeks, 3 rats in each group were sacrificed and compressed disc were analyzed.Results. After compression, the targeted CEP degenerated gradually with time. Through 12 weeks' loading, the CEP structure collapsed completely and the Schmorl's nodes formed and penetrated from the cartilage layer into the vertebra. When compared with the control group, the number of micro porosities in the CEP becomes extremely scarce with loading, while the content of aggrecan and collagen II decreased significantly. However, these significant changes did not show up when sham and control groups were compared.Conclusions. A new excessive force induced CEP degeneration animal model was developed with its contribution as a practical alternative for further studying mechanisms of CEP degeneration.

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Static Compression Induces ECM Remodeling and Integrin α2β1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model

Abstract: N/A.

Cited by 48 publications

References 52 publications

Mechanotransduction and cell biomechanics of the intervertebral disc

Mechanotransduction and cell biomechanics of the intervertebral disc

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

The Establishment of Intervertebral Endplate Degeneration: A Novel in-vivo Diurnal-Axial Controllable Loading Model in Rat Tail

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