ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

Gonzales, Silvia; Wang, Chong; Levene, Howard; Cheung, Herman S.; Huang, Chun Yuh

doi:10.1007/s00441-014-2042-2

Cited by 25 publications

(36 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously found a high extracellular accumulation of ATP at approximately 165 μM in the NP region [Wang et al, 2013], while 100 μM of extracellular ATP could effectively promote IVD cell ECM synthesis [Gonzales et al, 2015]. Since ATP is often rapidly hydrolyzed into adenosine by ectonucleotidases, a similar level (100 μM) of extracellular adenosine accumulation could be expected.…”

Section: Pg and Collagen Protein Measurementsmentioning

confidence: 86%

“…The cell-agarose constructs (8 mm in diameter and 2 mm thick) were made by mixing equal volumes of 2 × 10 7 cells/mL cell suspension and 4% agarose (Sigma-Aldrich) gel solution, and casting 100 µL of the mixture into individual wells of a custom designed mold. Therefore, the final concentration in each sample is 10 7 cells/mL in 2% agarose [Gonzales et al, 2015], which was then cultured at 37 ° C, 5% CO 2 in DMEM supplemented with 10% FBS and 1% antibiotic-antimycotic for 2 days before the experiment.…”

Section: Ivd Cells Isolation and Sample Preparationmentioning

confidence: 99%

“…All freshly isolated cells were placed into three-dimensional agarose culture. Three-dimensional agarose culture was chosen because it has been shown to prevent phenotypic changes of IVD cells [Gruber et al, 1997;Gonzales et al, 2015]. The cell-agarose constructs (8 mm in diameter and 2 mm thick) were made by mixing equal volumes of 2 × 10 7 cells/mL cell suspension and 4% agarose (Sigma-Aldrich) gel solution, and casting 100 µL of the mixture into individual wells of a custom designed mold.…”

Section: Ivd Cells Isolation and Sample Preparationmentioning

confidence: 99%

“…Our prior work has demonstrated that static and dynamic compressions promote ATP production and release by IVD cells Salvatierra et al, 2011]. Due to the avascular nature of the IVD, extracellular ATP was found to be accumulated in the nucleus pulposus (NP), which favors ECM production of IVD cells [Wang et al, 2013;Gonzales et al, 2015]. In addition, extracellular ATP is often hydrolyzed into adenine derivatives (i.e., ADP, AMP, and adenosine) by several families of ectonucleotidases, which include the E-NTPDases family, the E-NPPs family, alkaline phosphatase, and ecto-5′-nucleotidase/CD73 [Stefan et al, 2005;Robson et al, 2006;Yegutkin, 2008].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Effect of Adenosine on Extracellular Matrix Production in Porcine Intervertebral Disc Cells

Yin

Gonzales

Sha

et al. 2018

Cells Tissues Organs

Self Cite

View full text Add to dashboard Cite

Compressive loading promotes adenosine triphosphate (ATP) production and release by intervertebral disc (IVD) cells. Extracellular ATP can be rapidly hydrolyzed by ectonucleotidases. Adenosine, one of the adenine derivatives of ATP hydrolysis, can modulate diverse cellular actions via adenosine receptors. The objectives of this study were to investigate the effects of exogenous adenosine on the production of extracellular matrix (ECM; i.e., collagen type II and aggrecan) and ATP of IVD cells and explore the underlying mechanism of action. It was found that adenosine treatment significantly upregulated aggrecan and type II collagen gene expression and the ATP level in IVD cells. Dipyridamole, an adenosine transport blocker, completely suppressed the effects of adenosine on the ATP production and ECM gene expression of the IVD cells, whereas antagonists of adenosine receptors did not significantly affect adenosine-treated IVD cells. The findings suggested that elevated intracellular ATP and upregulation of ECM gene expression by adenosine treatment are mainly due to adenosine uptake rather than receptor activation. Since ECM biosynthesis is a high ATP demanding process, supplementing adenosine could be beneficial as IVD cells are able to utilize it to replenish intracellular ATP and sequentially promote ECM production, which is constantly suppressed by limited nutrition supply due to the avascular nature of the IVD.

show abstract

Section: Pg and Collagen Protein Measurementsmentioning

confidence: 86%

Section: Ivd Cells Isolation and Sample Preparationmentioning

confidence: 99%

Section: Ivd Cells Isolation and Sample Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Effect of Adenosine on Extracellular Matrix Production in Porcine Intervertebral Disc Cells

Yin

Gonzales

Sha

et al. 2018

Cells Tissues Organs

Self Cite

View full text Add to dashboard Cite

show abstract

“…Garcia and Knight suggested putative mechanism of ATP release via hemichannels (formed of connexin-43 subunits) in response to cyclic compression [131]. Since then a number of studies has shown that exogenous ATP supplementation, even in the absence of mechanical stimulation, can promote ECM biosynthesis and accumulation providing energy supply to fuel that process [132], increase mechanical properties, particularly through structural organization of the bulk phase and territorial ECM [133]. Exogenous ATP effects are proven to be dose-and time-dependent, where high doses can promote catabolic responses, necessitating the optimization of therapeutic dose range and application timing (e.g., transient vs. continuous) to the cell type and culture system [133][134][135].…”

Section: Purinergic Signalingmentioning

confidence: 99%

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Gadjanski

2018

Osteochondral Tissue Engineering

View full text Add to dashboard Cite

In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/ healing models and as in vitro models for drug toxicity/efficacy evaluation are covered. Highlights Biomimetic OC TE uses "smart" scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/ bone Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering Ivana GadjanskiAbstract In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue en...

show abstract

Towards engineering distinct multi‐lamellated outer and inner annulus fibrosus tissues

Santerre

Kandel

2017

Journal Orthopaedic Research

View full text Add to dashboard Cite

The annulus fibrosus (AF) of the intervertebral disc (IVD) has a zonal distribution of phenotypically distinct cells. The outer AF (OAF) cells produce an extracellular matrix (ECM) rich in type I collagen with little proteoglycans, whereas the ECM of the inner AF (IAF) has abundant type II collagen and proteoglycans. The inhomogeneous distribution of the ECM in the AF may reflect the complex mechanical forces that the IVD experiences. A bioengineered AF tissue should recapitulate both the inner and outer zones in order to have proper functionality. The aim of this study is to generate multi-lamellated OAF and IAF tissues with ECM compositions that resemble their zonal origin using polycarbonate urethane (PU) scaffolds. It was observed that supplementation of the media with insulin-transferrin-selenium (ITS) and proline yielded tissues with good cellularity. However, IAF cells accumulated only type I collagen, similar to OAF cells. Addition of dexamethasone and sodium pyruvate induced the accumulation of IAF tissues rich in type II collagen and aggrecan, without altering the accumulation of type I collagen in OAF tissues. Dexamethasone stimulated mitochondrial membrane potential in both tissues in the presence of sodium pyruvate, suggesting a relationship between the mitochondrial aerobic respiratory state and dexamethasone signalling during the in vitro-tissue formation by OAF and IAF cells. Inhibition of the glucocorticoid receptor blocked the stimulation of mitochondrial membrane potentials and type II collagen accumulation. In summary, biologically distinct multi-lamellated OAF and IAF tissues can be generated, which will facilitate advancement towards the goal of engineering a biological IVD replacement. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1346-1355, 2018.

show abstract

ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

Cited by 25 publications

References 46 publications

The Effect of Adenosine on Extracellular Matrix Production in Porcine Intervertebral Disc Cells

The Effect of Adenosine on Extracellular Matrix Production in Porcine Intervertebral Disc Cells

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Towards engineering distinct multi‐lamellated outer and inner annulus fibrosus tissues

Contact Info

Product

Resources

About