Mechanical loading affects the energy metabolism of intervertebral disc cells

Fernando, Hanan N.; Czamanski, Jessica; Yuan, Tai Yi; Gu, Weiyong; Abdi, Salahadin; Huang, Chun Yuh

doi:10.1002/jor.21430

Cited by 53 publications

(57 citation statements)

References 48 publications

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“…This difference in cellular responses to ATP between NP and AF cells could be explained by our previous study which found that NP cells reside in an environment with a higher level of extracellular ATP (~165 µM) than AF cells (<10 µM) (Wang, et al, 2013). Furthermore, our findings of higher PG and collagen accumulations and intracellular ATP content by the NP groups compared to the AF counterpart groups are consistent with our previous studies, which suggested that NP cells are more metabolically active than AF cells (Czamanski, et al, 2011, Fernando, et al, 2011). The differences in the metabolic activities between AF and NP cells may be explained by differences in cell phenotypes in which AF cells are elongated and resemble fibroblasts, whereas NP cells are spheroidal and chondrocyte-like (Buckwalter, 1995).…”

Section: Discussionsupporting

confidence: 93%

“…In our study, mRNA levels of aggrecan and type II collagen were upregulated by extracellular ATP, which also correlated with their corresponding protein synthesis. Since our previous studies have shown that static and dynamic loading alter ATP production and release in IVD cells (Czamanski, et al, 2011, Fernando, et al, 2011) and in-situ energy metabolism in the IVD (Wang, et al, 2013), the finding of this study suggests that mechanical loading may affect ECM production of IVD cells via an extracellular ATP pathway.…”

Section: Discussionsupporting

confidence: 50%

“…Our recent studies have demonstrated that compressive loading promotes ATP production and release in IVD cells in a 3-dimensional agarose gel model (Czamanski, et al, 2011, Fernando, et al, 2011) and in-situ energy metabolism in the IVD (Wang, et al, 2013). Furthermore, high accumulation of extracellular ATP due to the disc’s avascular nature was found in the center of young healthy porcine IVD (Wang, et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

et al. 2014

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A recent study by our lab found high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation may regulate biological activities in the IVD. Therefore, the objective of this study was to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: annulus fibrosus (AF) and nucleus pulposus (NP). The ATP treatment significantly promoted the ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in 3-dimensional agarose culture. A significant increase in ECM accumulation was found in AF cells at a lower ATP treatment level (20 µM) compared to NP cells (100 µM), indicating that AF cells may be more sensitive to extracellular ATP than NP cells. NP cells also exhibited higher ECM accumulation and intracellular ATP than AF cells under Control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, the ATP treatment also augmented the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via molecular pathway but also increases energy supply to fuel that process.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

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ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

et al. 2014

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“…The investigation of the effects of static and dynamic compressive loading on energy metabolism suggested that IVD cell energy production is affected in a cell type-and compression type-dependent manner; the total ATP content in the NP increased when 1 Hz dynamic loading was applied [95]. A trend of decreasing metabolic activity in the NP with increasing torsion magnitude was observed and the apoptotic activity in the NP significantly increased with 5°torsion [96].…”

Section: Mechanical Loading On Npcsmentioning

confidence: 98%

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

Shoukry

Pei

2013

Stem Cells and Development

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The nucleus pulposus (NP) plays a prominent role in both the onset and progression of intervertebral disc degeneration. While autologous repair strategies have demonstrated some success, their in vitro culture system is outdated and insufficient for maintaining optimally functioning cells through the required extensive passaging. Consequently, the final population of cells may be unsuitable for the overwhelming task of repairing tissue in vivo and could result in subpar clinical outcomes. Recent work has identified synovium-derived stem cells (SDSCs) as a potentially important new candidate. This population of precursors can promote matrix regeneration and additionally restore the balance of catabolic and anabolic metabolism of surrounding cells. Another promising application is their ability to produce an extracellular matrix in vitro that can be modified via decellularization to produce a tissue-specific substrate for efficient cell expansion, while retaining chondrogenic potential. When combined with hypoxia, soluble factors, and other environmental regulators, the resultant complex microenvironment will more closely resemble the in vivo niche, which further improves the cell capacity, even after extensive passaging. In this review, the adaptive mechanisms NP cells utilize in vivo are considered for insight into what factors are important for constructing a tissue-specific in vitro niche. Evidence for the use of SDSCs for NP regeneration is also discussed. Many aspects of NP behavior are still unknown, which could lead to future work yielding key information on producing sufficient numbers of a high-quality NPspecific population that is able to regenerate deteriorated NP in vivo.

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“…These cellular processes determine the quality and integrity of the ECM and thus, the mechanical response of the IVD 5 . Our recent studies have demonstrated that compressive loading affects ATP production and release by IVD cells in the 3-dimensional agarose gel model 6, 7 and in-situ energy metabolism in the IVD 8 . A high accumulated level of extracellular ATP (~165 μM) compared to physiological concentrations (1–50 nM) 9 has been found in the nucleus pulposus (NP) of the IVD 8 .…”

Section: Introductionmentioning

confidence: 98%

Measurement of ATP-Induced Membrane Potential Changes in IVD Cells

et al. 2014

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Extracellular adenosine-5'-triphosphate (ATP) triggers biological responses in a wide variety of cells and tissues and activates signaling cascades that affect cell membrane potential and excitability. It has been demonstrated that compressive loading promotes ATP production and release by intervertebral disc (IVD) cells, while a high level of extracellular ATP accumulates in the nucleus pulposus (NP) of the IVD. In this study, a noninvasive system was developed to measure ATP-induced changes in the membrane potential of porcine IVD cells using the potential sensitive dye di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS).The responses of NP and annulus fibrosus (AF) cells to ATP were examined in monolayer and 3-dimensional cultures. It was found that the pattern and magnitude of membrane potential change in IVD cells induced by extracellular ATP depended on cell type, culture condition, and ATP dose. In addition, gene expression of P2X4 purinergic receptor was found in both cell types. Inhibition of the ATP-induced response by pyridoxalphosphate-6-azophenyl-2', 4'-disulfonate (PPADS), a non-competitive inhibitor of P2 receptors, suggests that ATP may modulate the biological activities of IVD cells via P2 purinergic receptors.

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Mechanical loading affects the energy metabolism of intervertebral disc cells

Cited by 53 publications

References 48 publications

ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

Measurement of ATP-Induced Membrane Potential Changes in IVD Cells

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