Biophysics and Biochemistry of Cartilage by NMR and MRI: Volume 8 - Rilegato

Rilegato

ISBN 10: 1782621334 ISBN 13: 9781782621331

Casa editrice: Royal Society of Chemistry, 2016

Riassunto

This unique book describes the latest information in the fundamental understanding of the biophysics and biochemistry of articular cartilage using the state-of-the-art practices in NMR and MRI. This is the first book of its kind, written by physicists and chemists on this important tissue, whose degradation contributes to osteoarthritis and related joint diseases. Connecting the fundamental science with the clinical imaging applications, the experts Editors provide an authoritative addition to the literature.
Ideal for practising physical scientists and radiologists with an interest in the fundamental science as well as instrument manufacturers and clinical researchers working with articular cartilage.

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This unique book describes the latest information in the fundamental understanding of the biophysics and biochemistry of articular cartilage using the state-of-the-art practices in NMR and MRI. This is the first book of its kind, written by physicists and chemists on this important tissue, whose degradation contributes to osteoarthritis and related joint diseases. Connecting the fundamental science with the clinical imaging applications, the experts Editors provide an authoritative addition to the literature.
Ideal for practising physical scientists and radiologists with an interest in the fundamental science as well as instrument manufacturers and clinical researchers working with articular cartilage.

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Biophysics and Biochemistry of Cartilage by NMR and MRI

By Yang Xia, Konstantin I. Momot

The Royal Society of Chemistry

Copyright © 2017 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-78262-133-1

Contents

Part One – Introduction, 
Chapter 1 Introduction to Cartilage Yang Xia, Konstantin I. Momot, Zhe Chen, Christopher T. Chen, David Kahn and Farid Badar, 3, 
Chapter 2 Osmotic Properties of Cartilage Yang Xia, Konstantin I. Momot, Zhe Chen, Christopher T. Chen, David Kahn and Farid Badar, 44, 
Chapter 3 Introduction to NMR and MRI Konstantin I. Momot, 62, 
Chapter 4 The Magic Angle Effect in NMR and MRI of Cartilage Gary D. Fullerton, 109, 
Part Two – Cartilage Research by Experimental NMR and MRI Techniques, 
Chapter 5 Physical Properties of Cartilage by Relaxation Anisotropy Miika T. Nieminen, Mikko J. Nissi, Matti Hanni and Yang Xia, 147, 
Chapter 6 Chemical Properties of Cartilage Studied Using Charged Ions Olle Söderman, Jenny Algotsson, Leif E. Dahlberg and Jonas Svensson, 176, 
Chapter 7 Quantification of Articular Cartilage Microstructure by the Analysis of the Diffusion Tensor Monique C. Tourell, Sean K. Powell and Konstantin I. Momot, 191, 
Chapter 8 Sodium and Other Exotic Methods in NMR and MRI of Cartilage Ravinder Reddy and Arijitt Borthakur, 225, 
Chapter 9 Multi-Quantum Filtered NMR and MRI of Cartilage Hadassah Shinar and Gil Navon, 246, 
Chapter 10 Solid-State NMR Techniques to Study the Molecular Dynamics in Cartilage Daniel Huster, 279, 
Chapter 11 Ultrashort Echo Time Imaging of Articular Cartilage Soorena Azam Zanganeh, Hongda Shao, Graeme M. Bydder and Jiang Du, 299, 
Chapter 12 Low-Field and Field-Cycling NMR and MRI of Cartilage Siegfried Stapf, Carlos Mattea and Erik Rössler, 320, 
Chapter 13 The Influence of Specimen and Experimental Conditions on NMR and MRI of Cartilage ShaoKuan Zheng and Yang Xia, 347, 
Part Three – Biomechanical Properties of Cartilage by NMR and MRI, 
Chapter 14 Diffusion MRI and Poroelastic Biomechanics of Articular Cartilage Daniel Topgaard, 375, 
Chapter 15 Combining Multi-Modal MRI and Biomechanical Modeling to Investigate the Response of Cartilage and Chondrocytes to Mechanical Stimuli Luyao Cai, Corey P. Neu and David M. Pierce, 395, 
Chapter 16 Loading-Induced Changes in Cartilage Studied by NMR and MRI Nian Wang and Yang Xia, 433, 
Part Four – Applications and the Future of Cartilage Research by NMR and MRI, 
Chapter 17 The Critical Role of High Imaging Resolution in MRI of Cartilage—The MRI Microscope Yang Xia, 457, 
Chapter 18 Multicomponent Relaxation in NMR and MRI of Cartilage David A. Reiter, Richard G. Spencer and Yang Xia, 471, 
Chapter 19 Uni- and Multi-Parametric Magnetic Resonance Analysis of Cartilage Beth G. Ashinsky and Richard G. Spencer, 494, 
Chapter 20 Magnetic Resonance in the Assessment of Tissue Engineered Cartilage Mrignayani Kotecha, Ziying Yin and Richard L. Magin, 529, 
Chapter 21 Complementary Imaging in MRI of Cartilage Yang Xia and Jukka S. Jurvelin, 552, 
Chapter 22 Quantitative MRI for Detection of Cartilage Damage José G. Raya and Uran Ferizi, 575, 
Chapter 23 Challenges for the Early Detection of Degenerative Cartilage Changes Using Magnetic Resonance Imaging In vivo in Humans Matthew C. Gallo, Hsiang-Ling Teng and Sharmila Majumdar, 628, 
Chapter 24 Ultrahigh-Field Whole-Body MRI for Cartilage Imaging: Technical Challenges Matthew C. Gallo, Hsiang-Ling Teng and Sharmila Majumdar, 671, 
Subject Index, 706, 

CHAPTER 1

Introduction to Cartilage

YANG XIA, KONSTANTIN I. MOMOT, ZHE CHEN, CHRISTOPHER T. CHEN, DAVID KAHN AND BADAR

1.1 Introduction

Cartilage is a skeletal tissue that, together with the bone, forms the framework supporting the body as a whole. It is a tissue of great biological importance, which is apparent from the fact that vertebrate life would be impossible without cartilage: different types of cartilage play major roles in the function of such crucial systems as the spine and the respiratory system. Among different types of cartilage, articular cartilage is the best known and perhaps the most studied type. Articular cartilage is the thin layer of connective tissue that covers the articulating ends of bones in synovial joints (e.g., knee, hip, shoulder, and many other movable joints in the body). The intense interest in articular cartilage is motivated by the critical role its degradation plays in arthritis and related joint diseases, which are the number one cause of disability in humans.

This chapter provides an essential (albeit incomplete) introduction to the multi-level and multi-scale properties of articular cartilage that give this tissue its extraordinary load-bearing characteristics. Section 1.2 describes the general relationship between cartilage and the joint, while the following sections focus on different aspects of articular cartilage that are important to understanding its biological properties and its magnetic resonance behaviour. Sections 1.3-1.6 introduce cartilage at cellular, extracellular, histological and biomechanical levels. Sections 1.7-1.9 discuss the spatial heterogeneity of cartilage properties over the whole joint, diseases of cartilage and joint, and research into arthritis and related joint diseases.

1.2 Cartilage and the Joint

Cartilage is a specialised connective tissue present in animals, including humans, distinct from connective tissue proper. Cartilage tissue is stiff but also flexible. As a result, it is an integral part of many parts of the body where the supporting structures must accommodate limited movement.

1.2.1 Different Types of Cartilage

Different varieties of cartilage occur at specific anatomical locations. Three types of cartilage are commonly distinguished morphologically.

(1) Hyaline cartilage is named from the Latin word "hyalinus", meaning "smooth", "clear" or "glass-like". I t has a homogeneous appearance and a semi-solid consistency. H yaline cartilage is the most abundant type of cartilage in the body and includes articular cartilage, which lines the articulating surfaces of bones within many movable joints. Other varieties of hyaline cartilage include costal cartilage connecting the anterior ends of the ribs to the sternum, nasal cartilage, and many laryngeal and tracheobronchial cartilages. I n the foetus, hyaline cartilage forms most of the embryonic skeleton ("temporary cartilage") before it is replaced by bone during ossification. H yaline cartilage also forms epiphyseal growth plates, which enable rapid growth of long bones during childhood (see Section 1.3.1).1,4

(2) Fibrocartilage is fasciculated and fibrous. I t exhibits significant tensile strength and occurs in many areas subject to high mechanical stress. Fibrocartilage forms the annuli of intervertebral discs in the spine (anulus fibrosus), the menisci of the knee and certain other joints, and the plates connecting the opposing surfaces of bones within many immovable joints (e.g. the pubic symphysis). I t is also present in some movable joints (e.g. glenoid and acetabular labra) and at the bone attachment sites of tendons and ligaments. Finally, fibrocartilage is found in articular discs, which facilitate independent movements in certain compound joints (e.g. the distal radioulnar joint in the wrist)."

(3) Elastic cartilage is similar to hyaline cartilage, but exhibits greater elasticity. It is found in parts of the body where stretchability is required, most notably in the epiglottis – the elastic flap at the entrance to the larynx that acts as a valve allowing entry either into the trachea or the oesophagus. It is also present at the attachment of the vocal cords to the larynx and forms part of the structure of the external ear.

1.2.2 Synovial Joints and Articular Cartilage

Synovial joints are a certain type of joint that allow for a wide range of motion. They include the knee (Figure 1.1), hip, shoulder and elbow, as well as numerous smaller joints. The adjective "synovial" refers to the presence of a synovial cavity – a space enclosed by a dense, fibrous articular capsule filled with synovial fluid.

A synovial joint behaves in many ways as a "complete organ" (or more precisely, an organ system). Its biomechanical function is carried out by its many components functioning in conjunction with each other:

(1) Articular cartilage is a thin layer of connective tissue that covers the articulating surfaces of the bones within a synovial joint (see Figure 1.1). It protects the bone and processes mechanical load applied to the joint (see Section 1.6). The surface of the cartilage facing the synovial space is known as the articular surface. The articular surface is lubricated and exhibits very low friction.

(2) Synovial fluid is a filtrate of plasma that contains significant amounts of the polysaccharide hyaluronic acid (HA) and exhibits viscoelastic rheological properties. It contributes to the lubrication of the articular surface.

(3) The inner lining of the articular capsule is the synovial membrane, which is made up of loose connective tissue. The surface of the membrane is lined with squamous-to-cuboidal cells (synoviocytes) one to four layers deep. The cells are traditionally categorized into macrophage- like type A (which synthesize HA) and fibroblast-like type B (which synthesize various proteins). These two types are considered by some to be one cell population that alters its phenotype according to functional demands.

(4) Certain joints, most notably the knee, contain a meniscus – a fibrocartilaginous structure that fits between the articular surfaces of apposing bones and contributes to load processing.

(5) Ligaments and muscles provide transmission of mechanical forces across the joint and reinforce the synovial cavity and the joint itself.

The articular capsule of a synovial joint is vascularized, but the interior of the joint (synovial cavity) is an avascular (as well as aneural) environment. This has two major implications for articular cartilage:

(1) Articular cartilage is dependent upon the synovial fluid for the delivery of nutrients and the removal of metabolic wastes. Both these vital processes occur mainly via passive diffusion. The synovial lining lacks a basement membrane and merges with the underlying vascular connective tissue within the articular capsule; this allows for rapid exchange between blood and synovial fluid. Removal of particulate debris from the synovial cavity is performed by synoviocytes.

(2) The absence of a direct blood supply renders the repair of diseased or damaged cartilage slow and inefficient. This is a major biological factor contributing to the prevalence of osteoarthritis, a degenerative disease of articular cartilage discussed in Sections 1.8 and 1.9.

In the major joints of large animals and adult humans, the thickness of articular cartilage ranges from approximately 2 mm (bovine knee articular cartilage) to approximately 4 mm (human knee). Cartilage in smaller human joints and in many laboratory animals is much thinner. Histologically, articular cartilage is commonly subdivided into four distinct and parallel zones based on the local orientation of the collagen fibrils. These zones are the superficial zone, the transitional zone, the radial zone, and the calcified zone (Figure 1.2).

1.3 Cellular Aspects of Articular Cartilage

Articular cartilage has a low cellularity, with the living cells (chondrocytes) occupying only approximately 2% of the volume of mature human cartilage. The bulk of the tissue is the extracellular matrix (ECM), which depends crucially on this small number of chondrocytes to synthesize and maintain articular cartilage over the lifetime. The loss of the cells will induce fatigue to the ECM and eventually a failure of the joint.

1.3.1 Cartilage Progenitor Cells

Articular cartilage is formed through condensation of cartilage progenitor cells (CPCs). During the initial growth of articular cartilage, the CPCs in the growth plate (at the end of the bone) undergo a series of tightly regulated differentiation and maturation processes and can be found to have four morphologically distinct layers (the resting, proliferative, prehypertrophic, and hypertrophic layers); the cells in these layers have differences in gene expression pattern and function. The resting layer is the farthest layer from the bone and consists of undifferentiated CpCs, which are fusiform, compactly positioned, have a low rate of proliferation, and are smaller and denser than mature chondrocytes, with larger nuclei and less cytoplasm. In the proliferative layer, CpCs gain a proliferative phenotype and have an increased proliferation rate that results in a flattened and oblate shape, and arrangement of multicellular clusters into longitudinal columns. These highly organized columns may be directed by the cells in the resting layer, which have been postulated to produce a growth plate orientating factor. Both resting and proliferating cells can synthesize proteoglycans (e.g. versican) and collagens (e.g. type IIA), which have some distinctions while closely resembling those in mature articular cartilage.^ Following the proliferation layer, cells pass through a transition layer (prehypertrophic layer), in which they lose their proliferative ability and gradually increase in size due to swelling. Finally, these cells become hypertrophic and undergo major phenotypic changes,following a cascade of events including ECM mineralization, angiogenesis, and cellular apoptosis, which eventually lead to the formation of bone.

1.3.2 Mature Chondrocytes in Cartilage

Mature chondrocytes are the only cell type present in adult articular cartilage. Unlike the CPCs, mature chondrocytes normally maintain a stable phenotype. Mature chondrocytes vary in numbers, sizes (approximately 10-15 µm in diameter), and shapes (oval to circular), depending on the tissue zone in which they are located (Figure 1.2). There are a number of cellular gradients across the zones in cartilage. For example, the chondrocyte density per zone can increase from 7000 to 24 000 cells mm-3 along the tissue depth. Both cellular surface area per tissue volume and cellular volume per tissue volume have their maximum values in the upper radial zone.

Morphologically, the mature chondrocytes in the superficial zone are flattened, in single-cell units, and oriented in parallel to the articular surface. Mature chondrocytes in the transitional zone are more rounded and often found in pairs, while mature chondrocytes in the radial zone are rounded or elliptic individually and aligned as a multi-cell group along the collagen fibrils. Mature chondrocytes in the calcified cartilage become hypertrophic and synthesize collagen type X. Chondrocytes and their pericellular matrix in cartilage are organized as chondrons ("pericellular capsule") (Figure 1.3), which consist of the chondrocyte and the pericellular molecular proteins, of which collagen type VI and IX are the major components. These collagens are only present in close proximity to the cells, and decrease to a very low level away from the cells, where chondroitin sulfate and keratan sulfate become rich. The hollow spaces within the network that accommodate the chondrocytes are known as lacunae. Chondrons are the primary structural, functional, and metabolic units in articular cartilage.

Functionally, mature chondrocytes are highly specialized and responsible for synthesizing and remodeling the ECM (mainly comprised of collagen type II and aggrecan; see Section 1.4) which governs the functional and mechanical properties of articular cartilage. To produce and maintain healthy cartilage, the mature chondrocytes display a specific pattern of gene expression to both biochemical cues (e.g. interleukins (IL), insulin-like growth factors, bone morphogenetic protein, transforming growth factor, and fibroblast growth factor) and mechanical influences (e.g. compression, shear, and hydrostatic pressure; see also chapter 15) by various signal transduction mechanisms, such as integrins (e.g. a5ß1 and a2ß1) and ion channels (e.g. Ca2+) following Src and focal adhesion kinases, the Rho family of small GTPases, mitogen-activated protein kinase, phospholipase C and nuclear factor-?B pathways. Normal chondrocytes isolated from the different zones of articular cartilage show differences in proliferation rates and proteoglycan/collagen synthesis, and in their responses to cytokines. Generally, chondrocytes from the deeper zones show higher rates of proliferation and synthesis of collagen and proteoglycan compared with those from the superficial and middle zones, and those from the superficial zone are more sensitive to the catabolic effects of IL-1. However, in injured or diseased cartilage, chondrocytes have morphologic alterations and altered patterns of gene expression, which changes their ability to repair or maintain the ECM.

1.3.3 Mesenchymal Stem Cells

Since mature chondrocytes are terminally differentiated and seem unable to regenerate and replace damaged cartilage, mesenchymal stem cells (MSCs) have been used to develop engineered cartilage tissue. MSCs can be isolated from both adult and fetal tissues (e.g. bone marrow, blood, amniotic fluid, lung, liver, spleen, and umbilical cord) and differentiated towards multiple phenotypes (e.g. chondrogenic, osteogenic, adipogenic, and neural). Mature chondrocytes are the differentiated MSCs. A panel of surface markers has been developed to isolate and characterize MSCs, notably the expression of CD29, CD44, CD73, CD90, CD105, and CD166, and the absence of CD34 and CD45.

Mesenchymal stem cells are present in normal and osteoarthritic human articular cartilage. In cases of injury, tissue-specific MSCs in various adult tissues can proliferate, differentiate, and regenerate the damaged tissue. However, the percentage of these cells decreases with age, concomitant with a lower capacity for proliferation and differentiation. Fetal MSCs have an enhanced plasticity potential and proliferation propensity when compared with adult MSCs, since they have active telomerase and express pluripotency markers. In addition, fetal MSCs offer very low immunogenic properties, which can be explained by the low expression of human leukocyte antigen (HLA)-I and the lack of HLA-II expression. In addition, fetal MSCs isolated from different tissues exhibit heterogeneous multi-lineage differentiation potential. For example, fetal femoral head MSCs showed a higher adipogenic differentiation potential than fetal spine MSCs. Moreover, since variations in the differentiation potential of MSCs isolated from second-trimester fetal tissues were observed, the plasticity of fetal MSCs may be, in part, determined by or dependent on the gestational age. For these reasons, fetal MSCs seem to be the best candidates for use in cartilage regeneration.

1.4 Extracellular Matrix of Articular Cartilage

While chondrocytes synthesize the ECM of cartilage, the ECM provides the structural and physiological environment for the living chondrocytes. The ECM is also responsible for the remarkable biomechanical properties of articular cartilage discussed in Section 1.6 and elsewhere in this book. The chemical composition of the articular cartilage ECM differs between young and adult cartilage, with the compositional changes occurring primarily during fetal development and skeletal maturation. The major components of the ECM of adult human articular cartilage are collagen (15-20% of the wet weight (w.w.) of cartilage), proteoglycans (3-10% w.w.), and water (65-75% w.w.).

1.4.1 Collagen

Collagen is a structural protein and the main solid component of the cartilage ECM (about 1/2 to 2/3 of the dry weight of articular cartilage). More than 50 different types of collagen and collagen-like proteins occur in vertebrates, and some 28 types are found in humans, but the type of principal importance in adult articular cartilage is collagen type II. The molecular building block of collagens is the tropocollagen molecule, which contains three amino acid chains. The amino acid sequence in each chain consists of repeating blocks glycine-proline-Y or glycine-X-hydroxyproline, where X and Y can be any amino acid. The unusual glycine- and (hydroxy)proline-rich amino acid composition is responsible for the chains forming a "coiled-coil" assembly; each chain twists into a left-handed helix, and the three twisted chains are then twisted together in a right-handed triple helix (see Chapter 4, Figure 4.10). The resulting molecule has the geometry of a rod ~300 nm long and 1.5 nm in diameter (Figure 1.4a).

Collagen II is a fibrillar protein[dagger] the coiled-coil molecules are assembled, via a combination of covalent cross-linking and non-covalent interactions, into fibrils of a typical diameter 50-80 nm. The molecules forming a fibril are staggered by a distance of 67 nm (see Figure 1.4a), which gives collagen its characteristic striated appearance in high-resolution electron microscopy images and Bragg reflections in small-angle X-ray scattering. The fibrils form a cross-linked network that serves as the structural scaffold of the ECM of articular cartilage. The typical fibril-fibril separation within the network is a few hundred nanometers. Multiple collagen fibrils bundle into collagen fibers in tissues.

The collagen network of the articular cartilage's ECM is synthesized by the chondrocytes during skeletal growth. The synthesis virtually ceases in the adult articular cartilage. In the absence of an injury, the turnover time of collagen II in human femoral head cartilage has been estimated as several hundred years. The rate of collagen synthesis can increase by up to an order of magnitude following an injury; however, this is almost never sufficient to repair the damage

(Continues...)

Excerpted from Biophysics and Biochemistry of Cartilage by NMR and MRI by Yang Xia, Konstantin I. Momot. Copyright © 2017 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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Dettagli dell'edizione

• Editore: Royal Society of Chemistry
• Data di pubblicazione: 2016
• Lingua: Inglese
• ISBN 10: 1782621334
• ISBN 13: 9781782621331
• Rilegatura: Copertina rigida
• Numero di pagine: 731
• Redattore: Xia Yang, Momot Konstantin I.
• Contatto del produttore: non disponibile
• Persona responsabile: non disponibile