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Systems biology of osteoarthritis

Kamphorst, J.J.

Citation

Kamphorst, J. J. (2010, March 25). Systems biology of osteoarthritis.

Retrieved from https://hdl.handle.net/1887/15125

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/15125

Note: To cite this publication please use the final published version (if applicable).

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Systems Biology of Osteoarthritis

Proefschrift

ter verkrijging van

de graad van doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof. mr. P.F. van der Heijden, volgens besluit van het College voor Promoties

te verdedigen op donderdag 25 maart 2010 klokke 16.15 uur

Door

Jurre Jorian Kamphorst Geboren te Gouda

in 1981

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Promotiecommissie

Promotoren: Prof. Dr. T. Hankemeier Prof. Dr. J. van der Greef Dr. J. de Groot

Dr. R. van der Heijden

Overige leden: Prof. Dr. M. Danhof Prof. Dr. A.P. IJzerman Prof. Dr. F.P.J.G. Lafeber

Dr. G.P. Rozing

The Centre for Medical Systems Biology (CMSB) is gratefully acknowledged for funding the research described in this thesis.

Printing of this thesis was financially supported by Agilent Technologies and TNO Quality of Life.

The research described in this thesis was performed at the Division of Analytical Biosciences of the Leiden/Amsterdam Center for Drug Research, Leiden University, the Netherlands, in collaboration with the business unit Biosciences, TNO Quality of Life.

ISBN: 978-90-74538-71-8

This thesis was printed by Wӧhrmann Print Service (Zutphen, the Netherlands)

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Contents

1 General introduction and scope 5 2 Systems biology in osteoarthritis: omics-data

integration, biological interpretation and information-gap

identification 13

3 Profiling of endogenous peptides in human synovial fluid by nanoLC-MS: method validation and

peptide identification 33

4 Exploratory synovial fluid peptidomics for the

study of osteoarthritis 55

Appendix: Evaluation of a chip-based nanoLC platform for peptidomics biomarker studies 77 5 Feasibility of electrodialysis as a fast and selective sample

preparation method for the profiling of low-abundant peptides in biofluids 83 6 Lipid profiling reveals local as well as systemic changes

in lipid homeostasis during osteoarthritis 107

7 Conclusions and perspectives 127

Summary 133

Samenvatting 137

Curriculum Vitae 142

List of Publications 143

Nawoord 144

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