Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy Marieke de Mos Printing of this thesis was financially supported by Stichting Anna Fonds, Nederlandse Vereni- ging voor Matrix Biologie, Biomet, Reumafonds. ISBN: 978-90-8559-453-6 Cover by: Marieke de Mos Layout and printing: Optima Grafische Communicatie, Rotterdam, The Netherlands © M. de Mos, The Netherlands, 2008. All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means, without prior written permission by the author. Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy Peescelgedrag en matrix remodellering in degeneratieve tendinopathie Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. S.W.J. Lamberts en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 7 januari 2009 om 11.45 uur door Marieke de Mos geboren te Voorburg PRoMoTie CoMMissie Promotor: Prof.dr. J.A.N. Verhaar Overige leden: Prof.dr. J.M.W. Hazes Prof.dr. S.E.R. Hovius Prof.dr. P.R. Van Weeren Copromotor: Dr. G.J.V.M. van Osch Voor mama Contents List of Abbreviations 9 Chapter 1 General introduction 11 Chapter 2 Achilles tendinosis: changes in biochemical composition and 25 collagen turnover rate Chapter 3 Tendon degeneration is not mediated by regulation by Toll-like 43 receptors 2 and 4 in human tenocytes Chapter 4 Intrinsic differentiation potential of adolescent human tendon 55 tissue: an in-vitro cell differentiation study Chapter 5 In-vitro model to study chondrogenic differentiation in 73 tendinopathy Chapter 6 Can platelet-rich plasma enhance tendon repair: a cell culture study 89 Chapter 7 General discussion 105 Chapter 8 Summary 117 Appendices 123 Nederlandse samenvatting 125 Dankwoord 129 Curriculum Vitae 133 PhD Portfolio Summary 135 List of Publications 137 Color figures 139 List of Abbreviations α-SMA alpha smooth muscle actin AA Achilles tendon tissue adjacent to tendinotic lesion AGC1 aggrecan AGE advanced glycation endproduct AH healthy Achilles tendon tissue AT tendinotic Achilles tendon tissue BGLAP bone gamma-carboxyglutamate = osteocalcin BMSC bone marrow-derived stromal cell CBFA1 core-binding factor 1 = RUNX2 COL10A1 collagen type X, alpha 1 chain COL2A1 collagen type II, alpha 1 chain D7-FIB 11-fibrau, fibroblast antibody DMEM Dulbecco’s modified Eagle’s medium ECM extracellular matrix EGF epidermal growth factor FABP adipocyte fatty acid binding protein FACS fluorescense activated cell sorter FCS fetal calf serum FGF fibroblast growth factor GAG glycosaminoglycan HGF hepatocyte growth factor HP hydroxylysylpyridinoline HPLC high-performance liquid chromatography Hyl hydroxylysine Hyp hydroxyproline IGF insulin-like growth factor IHC immunohistochemistry IL interleukin LP lysylpyridinoline MEC medical ethical committee MMP matrix-metalloproteinase OA osteoarthritis PDGF platelet-derived growth factor PPARG peroxisome proliferative activated receptor gamma PPCR platelet-poor clot releasate PPP platelet-poor plasma PRCR platelet-rich clot releasate PRP platelet-rich plasma QPCR quantitative polymerase chain reaction RA rheumatoid arthritis RFU relative fluorescence unit RT-PCR reverse transcriptase polymerase chain reaction RUNX2 RUNT-related transcription factor 2 = CBFA1 SOX9 SRY-box 9 SP7 Sp7 transcription factor = osterix TDF tendon-derived fibroblast TGF transforming growth factor TLR Toll-like receptor TNF tumor necrosis factor VEGF vascular endothelial-derived growth factor A ns o ati vi e br b A of List 10
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