Identification of important interactions between subchondral bone ...

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Acknowledgements Acknowledgements First, I would like to acknowledge the Ministry of Science, Technology and Innovation (VTU) and Nordic Bioscience A/S, who funded this industrial Ph.D project. I would like to thank my supervisors Morten Asser Karsdal from Nordic Bioscience and Søren Tvorup Christensen from the University of Copenhagen, who have both provided great scientific guidance and enthusiasm throughout the project and writing process. I would also like to thank the co-supervisors, Anne-Christine Bay-Jensen and Kim Henriksen, for their support, excellent coaching, and helpful scientific discussions throughout my time at Nordic Bioscience. Furthermore, I would like to thank all my colleagues at Nordic Bioscience for helpful comments, technical help, scientific discussions, good times, and for creating a warm and pleasant work environment. Finally, I would like to thank my family and friends who have always supported my dreams and ambitions. Especially, I would like to thank Rasmus Klinck, for critical proofreading of my thesis, as well as for good friendship and support throughout my thesis. __________________________________ Suzi Høgh Madsen November 2011 2
Preface Preface The work presented in this thesis was performed in collaboration between Nordic Bioscience A/S and the University of Copenhagen under the industrial PhD agreement and with the supervision of Prof. Morten Asser Karsdal (company supervisor), Dr. Anne-Christine Bay Jensen (project supervisor, company), Dr. Kim Henriksen (project supervisor, company), and Associate Prof. Søren Tvorup Christensen (university supervisor). The work was carried out in the period ranging from October 2008 to November 2011. The PhD work includes four original research papers listed below. Three papers have been accepted and published, and one is under review. The individual articles are referred to in the present thesis by their roman numerals. The PhD thesis consists of an introduction to the topics of the four papers, the four papers, and a general conclusion. Paper I: Characterization of an Ex vivo Femur Head Model Assessed by Markers of Bone and Cartilage Turnover Suzi Hoegh Madsen, Anne Sofie Goettrup, Gedske Thomsen, Søren Tvorup Christensen, Nikolaj Schultz, Kim Henriksen, Anne-Christine Bay-Jensen, and Morten Asser Karsdal Cartilage 2011;2(3):265–278 Paper II: Glucocorticoids exert context-dependent effects on cells of the joint in vitro Suzi H. Madsen, Kim V. Andreassen, Søren T. Christensen, Morten A. Karsdal, Francis M. Sverdrup, Anne-Christine Bay-Jensen, and Kim Henriksen Steroids 2011;76(13):1474-1482 Paper III: Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo Suzi Hoegh Madsen, Eren Ufuk Sumer, Anne-Christine Bay-Jensen, Bodil-Cecilie Sondergaard, Per Qvist, and Morten Asser Karsdal Biomarkers 2010;15(3):266-276 Paper IV: Metalloproteinase and cysteine protease profiling in normal and Osteoarthritic cartilage Suzi Hoegh Madsen, Kim Henriksen, Søren Tvorup Christensen, Morten Asser Karsdal, and Anne Christine Bay-Jensen In review in Proteome Science The industrial PhD project has been supported by the Ministry of Science, Technology and Innovation (VTU) (08-036109) and Nordic Bioscience A/S. 3
Page 1 and 2: F A C U L T Y O F S C I E N C E U N
Page 3: Supervisors University of Copenhage
Page 7 and 8: Contents Contents Abstract ........
Page 9 and 10: Abstract Abstract Osteoarthritis (O
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Page 13 and 14: CHAPTER 1 Objectives CHAPTER 1: Obj
Page 15 and 16: CHAPTER 2 Introduction CHAPTER 2: I
Page 17 and 18: 2.2 Biology of the joint CHAPTER 2:
Page 19 and 20: CHAPTER 2: Introduction Also osteob
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Page 23 and 24: CHAPTER 2: Introduction When the jo
Page 25 and 26: CHAPTER 2: Introduction Cartilage i
Page 27 and 28: 2.3 The pathology of Osteoarthritis
Page 29 and 30: CHAPTER 2: Introduction number of a
Page 31 and 32: CHAPTER 2: Introduction Cysteine pr
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Page 35 and 36: 2.4 The effect of Glucocorticoids C
Page 37 and 38: 2.5 References for CHAPTER 2 1 WebM
Page 39 and 40: 51 Lorenz H. and Richter W. Osteoar
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Page 45 and 46: CHAPTER 3 Overview of OA models CHA
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Page 49 and 50: 3.3 Ex vivo controls CHAPTER 3: Ove
Page 51 and 52: 19 Brandt K.D. Animal models of ost
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266 Cartilage 2(3) therapy for oste
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268 Cartilage 2(3) Figure 1. Charac
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270 Cartilage 2(3) Figure 4. The ca
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272 Cartilage 2(3) Figure 5. Cytoki
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274 Cartilage 2(3) Figure 6. The an
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276 Cartilage 2(3) supports the inc
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278 Cartilage 2(3) release and rece
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CHAPTER 5 CHAPTER 5: PAPER II PAPER
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leading to fragility fractures [12]
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after 1 week (Fig. 2F). The additio
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use a range of assays ranging from
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still some controversy regarding th
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CHAPTER 6 CHAPTER 6: PAPER III PAPE
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Biomarkers Downloaded from informah
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CHAPTER 7 CHAPTER 7: PAPER IV PAPER
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Introduction CHAPTER 7: PAPER IV Ca
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Bovine articular cartilage experime
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CHAPTER 7: PAPER IV Detection of ke
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CHAPTER 7: PAPER IV The MMP inhibit
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CHAPTER 7: PAPER IV The pre-stimula
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CHAPTER 8 CHAPTER 8: General discus
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Future perspectives CHAPTER 8: Futu
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Appendix I Co-author declarations f
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Appendix I 107
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Appendix I 109
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Appendix I 111
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Biochemical Markers of Joint Tissue
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