Selected results and technologies exploited by the Consortium in Disc4All

 

LDD and LBP Cohort studies

Hartvigsen, J. et al. What low back pain is and why we need to pay attention. Lancet (London, England) 391, 2356–2367 (2018).

Munir, S., Rade, M., Määttä, J. H., Freidin, M. B. & Williams, F. M. K. Intervertebral Disc Biology: Genetic Basis of Disc Degeneration. Curr. Mol. Biol. Reports 4, 143–150 (2018).

Määttä, J. H. et al. Strong association between vertebral endplate defect and Modic change in the general population. Sci. Rep. 8, 1–8 (2018).

Munir, S. et al. Endplate Defect Is Heritable, Associated With Low Back Pain and Triggers Intervertebral Disc Degeneration: A Longitudinal Study From TwinsUK. Spine (Phila. Pa. 1976). 43, 1496–1501 (2018).

Williams, F. M. K. et al. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: A meta-analysis of 4600 subjects. Ann. Rheum. Dis. 72, 1141–1148 (2013).

Takatalo, J. et al. Body mass index is associated with lumbar disc degeneration in young Finnish males: subsample of Northern Finland birth cohort study 1986. BMC Musculoskelet. Disord. 14, 87 (2013).

Eskola, P. J. et al. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration: A three-year follow-up. Int. J. Mol. Epidemiol. Genet. 3, 195–204 (2012).

Williams, F. M. K. & Sambrook, P. N. Neck and back pain and intervertebral disc degeneration: role of occupational factors. Best Pract. Res. Clin. Rheumatol. 25, 69–79 (2011).

Williams, F. M. K. et al. GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arthritis Rheum. 63, 708–712 (2011).

Kelempisioti, A. et al. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults. BMC Med. Genet. 12, 153 (2011).

Livshits, G. et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: The UK Twin Spine Study. Ann. Rheum. Dis. 70, 1740–1745 (2011).

Karppinen, J. et al. Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men. Eur. Spine J. 18, 1963–1970 (2009).

Takatalo, J. et al. Prevalence of degenerative imaging findings in lumbar magnetic resonance imaging among young adults. Spine (Phila. Pa. 1976). 34, 1716–21 (2009).

Karppinen, J. et al. Genetic factors are associated with modic changes in endplates of lumbar vertebral bodies. Spine (Phila. Pa. 1976). 33, 1236–41 (2008).

 

IVD Biology & Experimental models

Bournonville, S. et al. Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture. Biotechnol. J. 14, 1800545 (2019).

Krupkova O, Sadowska A, Kameda T, Hausmann O, Klasen J, Wuertz-Kozak K: p38 MAPK facilitates crosstalk between endoplasmic reticulum stress and IL-6 release in the intervertebral disc. Frontiers in Immunology, 2018 Aug 17;9:1706

Franco-Obregón A, Cambria E, Greutert H, Wernas T, Egli M, Sekiguchi M, Boos N, Hausmann ON, Ferguson SJ, Kobayashi H, Wuertz-Kozak K: TRPC6 in simulated microgravity of intervertebral disc cells. Eur Spine J., 2018 Oct;27(10):2621-2630

Tekari, A., Chan, S. C. W., Sakai, D., Grad, S., & Gantenbein, B. (2016). Angiopoietin-1 receptor Tie2 distinguishes multipotent differentiation capability in bovine coccygeal nucleus pulposus cells. Stem Cell Res Ther, 7(1), 75. http://doi.org/10.1186/s13287-016-0337-9.

Schmocker AM, Khoushabi A, Frauchiger DA, Gantenbein B, Schizas C, Moser C, Bourban P-E, Pioletti D (2016) A photopolymerized Poly-Ethlyene-Glycol composite hydrogel and surgical implanting tool for a nucleus pulposus replacement. Biomaterials 88110-119 doi: 10.1016/j.biomaterials.2016.02.015.

Gantenbein B, Illien-Jünger S, Chan SC, Walser J, Haglund L, Ferguson SJ, Iatridis JC, Grad S (2015) Organ Culture Bioreactors - Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy. Curr Stem Cell Res Ther 10(4):339-352.

Phillips KLE, Chiverton N, Michael ALR, Cole AA, Breakwell LM, Haddock G, Bunning RAD, Cross AK, Le Maitre CL (2015). Potential Roles of Cytokines and Chemokines in Human Intervertebral Disc Degeneration: Interleukin-1 is a Master Regulator of catabolic processes. Osteoarthritis and cartilage.  23(7):1165-77.

Chan, S. C. W., Tekari, A., Benneker, L. M., Heini, P. F., & Gantenbein, B. (2015). Osteogenic differentiation of bone marrow stromal cells is hindered by the presence of intervertebral disc cells. Arthritis Res Ther, 18(1), 29. http://doi.org/10.1186/s13075-015-0900-2.

Binch ALA, Cole AA, Breakwell LM, Michael ALR, Chiverton N, Cross AK, Le Maitre CL. (2014). Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration. Arthritis Research and Therapy. 16(5): 416.

Phillips KLE, Chiverton N, Michael ALR, Cole AA, Breakwell LM, Haddock G, Bunning RAD, Cross AK, Le Maitre CL (2013). The Cytokine and chemokine expression profile of nucleus pulposus cells: implications for degeneration and regeneration of the Intervertebral disc. Arthritis Research and Therapy. 15: R213.

Wuertz, K. & Haglund, L. Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain. Glob. Spine J. 3, 175–184 (2013).

Chan SC, Walser J, Käppeli P, Shamsollahi M, Ferguson SJ, Gantenbein-Ritter B Region specific response of the intervertebral disc cells to complex dynamic loading (2013) An organ culture study using a bi-axial loading bioreactor. PLoS ONE 2013; 8:e72489

Le Maitre, C. L. et al. Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs. Arthritis Rheum. 60, 460–469 (2009).

Le Maitre CL, Freemont AJ, Hoyland JA. (2005) The Role of Interleukin 1 (IL-1) in the pathogenesis of human Intervertebral disc (IVD) degeneration. Arthritis Research and Therapy.7: R732-R745.

Wuertz K, Godburn K, MacLean JJ, Barbir A, Donnelly JS, Roughley PJ, Alini M, Iatridis JC: In vivo remodeling of intervertebral discs in response to short- and long-term dynamic compression.  J Orthop Res. 2009 Sep;27(9):1235-42

 

 

Models & Simulations

Schivo, S. et al. ECHO, the executable CHOndrocyte: A computational model to study articular chondrocytes in healthy and disease. Cell. Signal. 109471 (2019) doi:10.1016/j.cellsig.2019.109471.

Baumgartner, L., Reagh, J. J., González Ballester, M. A. & Noailly, J. Simulating intervertebral disc cell behavior within 3D multifactorial environments. bioRxiv (2019) doi:10.1101/2019.12.23.886887.

Ruiz Wills, C., Foata, B., González Ballester, M. Á., Karppinen, J. & Noailly, J. Theoretical Explorations Generate New Hypotheses About the Role of the Cartilage Endplate in Early Intervertebral Disk Degeneration. Front. Physiol. 9, 1–12 (2018).

Ceresa, M., Olivares, A. L., Noailly, J. & Ballester, M. A. G. Coupled immunological and biomechanical model of emphysema progression. Front. Physiol. 9, (2018).

Fotis, C., Antoranz, A., Hatziavramidis, D., Sakellaropoulos, T. & Alexopoulos, L. G. Network-based technologies for early drug discovery. Drug Discov. Today 23, 626–635 (2018).

Antoranz, A., Sakellaropoulos, T., Saez-Rodriguez, J. & Alexopoulos, L. G. Mechanism-based biomarker discovery. Drug Discov. Today 22, 1209–1215 (2017).

Olivares, A. L., González Ballester, M. A. & Noailly, J. Virtual exploration of early stage atherosclerosis. Bioinformatics 32, 3798–3806 (2016).

Kerkhofs, J. et al. A qualitative model of the differentiation network in chondrocyte maturation: A holistic view of chondrocyte hypertrophy. PLoS One 11, 1–27 (2016).

Ruiz Wills, C. et al. Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc. J. Mech. Phys. Solids 90, (2016).

Mangado, N., Piella, G., Noailly, J., Pons-Prats, J. & Ballester, M. Á. G. Analysis of Uncertainty and Variability in Finite Element Computational Models for Biomedical Engineering: Characterization and Propagation. Front. Bioeng. Biotechnol. 4, (2016).

Malandrino, A. et al. On the relative relevance of subject-specific geometries and degeneration-specific mechanical properties for the study of cell death in human intervertebral disk models. Front. Bioeng. Biotechnol. 3, (2015).

Malandrino, A., Jackson, A. R., Huyghe, J. M. & Noailly, J. Poroelastic modeling of the intervertebral disc: A path toward integrated studies of tissue biophysics and organ degeneration. MRS Bull. 40, (2015).

Melas, I. N. et al. Modeling of signaling pathways in chondrocytes based on phosphoproteomic and cytokine release data. Osteoarthr. Cartil. 22, 509–518 (2014).

Malandrino, A. et al. The role of endplate poromechanical properties on the nutrient availability in the intervertebral disc. Osteoarthr. Cartil. 22, (2014).

Kerkhofs, J., Roberts, S. J., Luyten, F. P., Van Oosterwyck, H. & Geris, L. Relating the Chondrocyte Gene Network to Growth Plate Morphology: From Genes to Phenotype. PLoS One 7, e34729 (2012).

 

Tools

López Picazo, M., Humbert, L., Di Gregorio, S., González Ballester, M. A. & del Río Barquero, L. M. Discrimination of osteoporosis-related vertebral fractures by DXA-derived 3D measurements: a retrospective case-control study. Osteoporos. Int. 30, 1099–1110 (2019).

Lopez Picazo M, Magallon Baro A, Del Rio Barquero LM, Di Gregorio S, Martelli Y, Romera J, Steghofer M, Gonzalez Ballester MA, Humbert L. 3D Subject-Specific Shape and Density Estimation of the Lumbar Spine from a Single Anteroposterior DXA Image Including Assessment of Cortical and Trabecular Bone, IEEE Trans Med Imaging. 2018 Dec;37(12):2651-2662.

Gutiérrez-Sacristán, A. et al. comoRbidity: an R package for the systematic analysis of disease comorbidities. Bioinformatics 34, 3228–3230 (2018).

Piñero, J. et al. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 45, D833–D839 (2017).

Jamaludin, A., Kadir, T. & Zisserman, A. SpineNet: Automated classification and evidence visualization in spinal MRIs. Med. Image Anal. 41, 63–73 (2017).

Jamaludin, A. et al. ISSLS PRIZE IN BIOENGINEERING SCIENCE 2017: Automation of reading of radiological features from magnetic resonance images (MRIs) of the lumbar spine without human intervention is comparable with an expert radiologist. Eur. Spine J. 26, 1374–1383 (2017)

Muñoz-Ruiz, M. Á. et al. Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer’s Disease. Dement. Geriatr. Cogn. Dis. Extra 6, 313–329 (2016).

Emili L., Baretta A., Serano P., Carbone V., Angelone L., Horner M., A Web-Based Platform for Simulating MRI RF-Induced Heating with Implanted Devices, BMES/FDA 2017 Frontiers in Medical Devices Conference, May 16-18, 2017, Washington, DC, U.S.A.

Casoni, E. et al. Alya: Computational Solid Mechanics for Supercomputers. Arch. Comput. Methods Eng. 22, 557–576 (2015).

Rubio-Campillo, X. Pandora : A Versatile Agent-Based Modelling Platform for Social Simulation. Proc. 6th Int. Conf. Adv. Syst. Simul. 29–34 (2014) doi:10.13140/2.1.5149.4086.

Mattila, J. et al. A disease state fingerprint for evaluation of alzheimer’s disease. J. Alzheimer’s Dis. 27, 163–176 (2011).

M. Vousden, M.A. Bisotti, M. Albert, H. Fangohr. Virtual Micromagnetics: A Framework for Accessible and Reproducible Micromagnetic Simulation. Journal of Open Research Software, 4(1), p.e41 (2016). 10.5334/jors.141