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Macrophage

phenotypes

in degenerative

joint diseases

lizette

utomo

Macr

ophage phenotypes in degener

ative joint dise

ases

li

z

e

t

t

e

u

t

o

m

o

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Macrophage Phenotypes in Degenerative

Joint Diseases

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Colofon

Copyright © Lizette Utomo, the Netherlands, 2018. ISBN: 978-94-6361-104-6

All rights reserved. No part of this thesis may be reproduced, distributed, stored in a retrieval system, or transmitted in any form or by any means, without the written permission of the author or, when appropriate, the publisher of the publications.

The work presented in this thesis was conducted at the Department of Orthopaedics, Erasmus MC University Medical Center Rotterdam, the Netherlands

Cover design: Lizette Utomo and Erwin Timmerman

Layout and printing: Optima Grafische Communicatie, Rotterdam, the Netherlands

Printing of this thesis was financially supported by:

Department of Orthopaedics, Erasmus MC University Medical Center Rotterdam Erasmus University Rotterdam

Netherlands Society for Biomaterials and Tissue Engineering (NBTE) Anna Fonds Leiden

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Macrophage Phenotypes in Degenerative Joint Diseases

Macrofaag fenotypen in degeneratieve gewrichtsaandoeningen

Proefschrift

ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam

op gezag van de rector magnificus Prof.dr. R.C.M.E. Engels

en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op

Dinsdag 18 september 2018 om 13:30 uur

door

Lizette Utomo geboren te Rotterdam

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ProMotieCoMMissie

Promotoren: Prof. dr. G.J.V.M. van Osch

Prof. dr. J.A.N. Verhaar

Overige leden: Prof. dr. C.C. Baan

Prof. dr. F.J. van Kemenade Dr. P.L.E.M. van Lent

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tabLe of Contents

Chapter 1 General introduction, thesis aim and outline 7 Chapter 2 Expression of CCL2 in synovium is inversely correlated with

articular cartilage degeneration in hip osteoarthritis patients

19

Chapter 3 Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages

33

Chapter 4 Macrophage phenotypes profiles during the course of osteoarthritis and their association with osteoarthritis features in two mouse models

49

Chapter 5 Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis

69

Chapter 6 Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro

93

Chapter 7 In vitro modulation of the behavior of adhering macrophages

by medications is biomaterial-dependent

121

Chapter 8 General discussion 145

Chapter 9 Summary 157 references 163 appendices 181 Nederlandse samenvatting 183 List of abbreviations 187 List of publications 189 Dankwoord 191 PhD portfolio 195 Curriculum vitae 199

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