Table Of ContentARTICULAR
CARTILAGE
S E C O N D E D I T I O N
ARTICULAR
CARTILAGE
S E C O N D E D I T I O N
Kyriacos A. Athanasiou
Eric M. Darling
Grayson D. DuRaine
Jerry C. Hu
A. Hari Reddi
CRC Press
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Library of Congress Cataloging‑in‑Publication Data
Names: Athanasiou, K. A. (Kyriacos A.), author. | Darling, Eric M., author. |
Hu, Jerry C., author. | DuRaine, Grayson D., author. | Reddi, A. H., 1942-
author.
Title: Articular cartilage / Kyriacos A. Athanasiou, Eric M. Darling, Jerry
C. Hu, Grayson D. DuRaine, and A. Hari Reddi.
Description: Second edition. | Boca Raton : Taylor & Francis, 2016. |
Preceded by Articular cartilage / Kyriacos A. Athanasiou ... [et al.].
2013. | Includes bibliographical references and index.
Identifiers: LCCN 2016021888 | ISBN 9781498706223 (alk. paper)
Subjects: | MESH: Cartilage, Articular
Classification: LCC QM142 | NLM WE 300 | DDC 612.7/517--dc23
LC record available at https://lccn.loc.gov/2016021888
Visit the Taylor & Francis Web site at
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To Thasos and Aristos, please remember that pursuit of excellence is the
virtuous objective.
Αφιερωμένο στους Θάσο και Άριστο. Αίεν αριστεύειν. —KAA
To my past and present mentors, who have contributed to my professional
success, and to my friends and family, who have contributed to my success
in everything else. —EMD
To Irene, Demitri, and Donovan, who make this all worthwhile. —GDD
To my family, my friends, and our past and current students; I think of
everyone on my treks, and wish that you could see what I see. —JCH
I dedicate this to Professor Kyriacos Athanasiou, a pioneer in articular
cartilage biomechanics and tissue engineering. —AHR
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Contents
Foreword to Second Edition ............................................................... xv
Foreword to First Edition ....................................................................xix
Authors .............................................................................................xxv
List of Abbreviations.........................................................................xxix
Chapter 1 Structure and Function of Cartilage .............................. 3
1.1 Cartilage in the Body ................................................................... 4
1.1.1 Hyaline .............................................................................. 4
1.1.2 Elastic ................................................................................ 6
1.1.3 Fibrous .............................................................................. 8
1.1.4 Cartilage’s Role in the Joints ............................................. 8
1.2 Chondrocytes and Their Cellular Characteristics ....................... 11
1.2.1 Genetic, Synthetic, and Mechanical Phenotype .............. 11
1.2.2 Cytoskeletal Structure ..................................................... 15
1.2.2.1 Microflaments ..................................................... 16
1.2.2.2 Intermediate Filaments ........................................ 17
1.2.2.3 Microtubules ....................................................... 17
1.2.3 Mechanotransduction and Homeostasis
in Cartilage Tissue ........................................................... 18
1.2.4 Pericellular Matrix Structure ............................................ 25
1.3 Cartilage Matrix Characteristics and Organization ..................... 27
1.3.1 Fluid Components ........................................................... 28
1.3.2 Zonal Variation within Cartilage ....................................... 30
1.3.2.1 Articulating Surface ............................................ 31
1.3.2.2 Superfcial/Tangential Zone ................................ 32
1.3.2.3 Middle/Transitional Zone ..................................... 32
1.3.2.4 Deep/Radial Zone ............................................... 32
1.3.2.5 Tidemark and Calcifed Zone .............................. 33
1.3.3 Collagens in Cartilage ..................................................... 34
1.3.3.1 Tissue-Level Organization .................................. 38
1.3.3.2 Collagen Cross-Linking and Biomechanical
Properties ........................................................... 40
vii
Contents
1.3.4 Cartilaginous Proteoglycans ............................................ 42
1.3.4.1 Core Proteins and Glycosaminoglycans ............. 42
1.3.4.2 Aggrecan’s Role in Articular Cartilage
Compressive Properties ..................................... 47
1.3.4.3 Minor Proteoglycans ........................................... 47
1.3.5 Additional Molecules Critical for Articular
Cartilage Function ........................................................... 48
1.3.5.1 Boundary Lubrication by SZP/PRG4 .................. 49
1.3.5.2 Molecules for Structural Integrity ........................ 51
1.4 Articular Cartilage Biomechanical Properties ............................ 51
1.4.1 Compressive Characteristics ........................................... 54
1.4.2 Tensile Characteristics .................................................... 57
1.4.3 Shear Characteristics ...................................................... 59
1.4.4 Friction and Wear Characteristics .................................... 60
1.5 Chapter Concepts ...................................................................... 63
References ........................................................................................64
Chapter 2 Articular Cartilage Development ................................. 83
2.1 Cellular Behavior during Embryogenesis ................................... 88
2.1.1 Limb Precursor Cell Origin .............................................. 88
2.1.1.1 Cell Adhesion Molecules .................................... 89
2.1.1.2 Initiation of Limb .................................................. 96
2.1.2 Chondrocyte Differentiation and Joint Development...... 106
2.1.2.1 Synovial Joint Formation ................................... 108
2.1.3 Tissue Hypertrophy and Ossifcation ............................. 109
2.2 Articular Cartilage Growth and Maturation ................................112
2.2.1 Postnatal through Childhood, Adolescence,
and Skeletal Maturity ......................................................112
2.2.2 Matrix Changes with Maturation and Aging ....................113
2.2.3 Aging and Disease .........................................................114
2.2.4 Cellular Changes ............................................................115
2.2.4.1 Aging Cells .........................................................115
2.3 Signaling Pathways during Development and Maintenance
of Articular Cartilage .................................................................117
viii
Contents
2.3.1 Signaling Factors ............................................................117
2.3.1.1 Morphogens and Growth Factors ......................117
2.3.1.2 Mechanical Stimuli .............................................119
2.3.1.3 Oxygen Tension ................................................ 120
2.3.2 Signaling Cascades ....................................................... 121
2.3.2.1 Morphogen Signaling ........................................ 121
2.3.2.2 BMP/TGF-β Superfamily ................................... 121
2.3.2.3 Receptors and Smads ...................................... 123
2.3.2.4 MAPK and Rho GTPase Signaling
in Articular Cartilage ......................................... 126
2.3.3 Transcription Factors ..................................................... 134
2.3.4 Cartilage Homeostasis .................................................. 137
2.4 Chapter Concepts .................................................................... 139
References ...................................................................................... 141
Chapter 3 Articular Cartilage Pathology and Therapies ........... 163
3.1 Arthritis .................................................................................... 163
3.1.1 Osteoarthritis and Rheumatoid Arthritis ........................ 164
3.1.1.1 Osteoarthritis .................................................... 164
3.1.1.2 Rheumatoid Arthritis ......................................... 166
3.1.2 Etiology and Epidemiology ............................................ 167
3.1.2.1 Genetic and Metabolic Defects ......................... 169
3.1.2.2 Crystal Pathologies ........................................... 173
3.1.2.3 Biomechanics, Loading, and Injury ................... 175
3.1.2.4 Epidemiology .................................................... 184
3.1.3 Changes in the Matrix ................................................... 186
3.1.4 Cellular Changes ........................................................... 190
3.1.5 Costs of Arthritis ............................................................ 194
3.2 Cartilage Injuries ...................................................................... 195
3.2.1 Osteochondral and Chondral Defects
and Microfractures ......................................................... 195
3.2.2 Causes of Cartilage Injuries .......................................... 200
3.2.3 Cellular Responses to Injury .......................................... 203
3.2.4 Costs of Articular Cartilage Injuries ............................... 205
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