11Cartilage in normal and osteoarthritis conditions
Introduction
Articular cartilage is a specialized, avascular, aneural connective tissue that provides covering for the osseous components of diarthrodial joints. It serves as a load-bearing material, absorbs impact and is capable of sustaining shearing forces. The unique properties of this tissue are related to the composition and structure of its extracellular matrix, which is composed mainly of a high concentration of proteoglycans (aggrecan) entangled in a dense network of collagen fibers and a large amount of water. This tissue allows the frictionless motion of the joint, in which it absorbs and dissipates load. The articular cartilage is composed of a sparse population of cells, named chondrocytes, which are responsible for the synthesis and maintenance of the extracellular matrix.
Osteoarthritis (OA) is characterized by degradation and loss of articular cartilage, hypertrophic bone changes with osteophyte formation, subchondral bone remodeling, and, at the clinical stage of the disease, chronic inflammation of the synovial membrane. Its etiology, although not yet completely understood, appears to result from a complex system of interacting mechanical, biological, biochemical, molecular, and enzymatic feedback loops. The final common pathway of cartilage destruction results from a failure of chondrocytes to maintain a homeostatic balance between matrix synthesis and degradation. As the disease progresses, the degradative process eventually exceeds the anabolic one, leading to a progressive loss of cartilage and eburnation of bone. This appears to occur when the physiologic balance between the synthesis and degradation of the extracellular matrix favors catabolism. At the clinical stage of the disease, an inflammatory reaction involving the synovial membrane is often present. This process favors the synthesis of inflammatory mediators, which impact on cartilage matrix homeostasis by altering chondrocyte metabolism to enhance catabolism and reduce anabolism.
This chapter summarizes the pertinent data related to the molecules and factors involved in cartilage maintenance, remodeling, and during the progression of OA.
Section snippets
Structural organization
The cartilage matrix consists of macromolecules in which collagen and proteoglycans (aggrecan) are the main representatives. These components are highly ordered from the cartilage surface to the deepest layers. Cartilage is divided into four zones with different functions: the superficial, middle or transitional, deep or radial, and calcified cartilage zones. Interestingly, there is no sharp boundary between the first three zones.
The superficial zone, the thinnest of the four, consists of fine
Subchondral bone and cartilage crosstalk in osteoarthritis
Although the initiating event responsible for the degradation of cartilage in OA patients remains elusive, the concept of a key role of the subchondral bone tissue in OA is gaining strong support. A plausible hypothesis is that cytokines, growth factors, and eicosanoids produced locally by subchondral bone tissue seep through the bone–cartilage interface and induce changes in the cartilage metabolism. Although it was previously thought that the calcified cartilage layer was an impenetrable
Biological markers of cartilage
When a component of joint tissue is released, measuring its concentration in the joint fluid is theoretically the most reliable approach. However, joint fluid collection is difficult in many OA patients and can be obtained readily only in the knee. Moreover, joint lavage results in significant errors to the concentration of the markers because of uncontrolled sample dilution. The best use of biomarkers in OA is their determination in serum or urine. However, their use in clinical practice has
Conclusion
Cartilage matrix turnover is mediated by a multitude of factors that act on the chondrocytes and could lead to repair, remodeling or catabolic processes. The molecules and factors involved in cartilage repair and maintenance have been the subject of intensive research and significant progress has been made in the understanding of the interactions of the components of this tissue. At a certain point, these processes are altered, resulting in matrix changes including local abnormal biochemical
References (188)
- et al.
Procollagen N-proteinase and procollagen C-proteinase. Two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling
Matrix Biology
(1998) - et al.
Effect of collagen turnover on the accumulation of advanced glycation end products
The Journal of Biological Chemistry
(2000) - et al.
Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding
The Journal of Biological Chemistry
(1992) - et al.
Ultrastructural localization of type VI collagen in normal adult and osteoarthritic human articular cartilage
Osteoarthritis and Cartilage
(2002) - et al.
Expression of type VI collagen in normal and osteoarthritic human cartilage
Osteoarthritis and Cartilage
(1999) - et al.
The folded modules of aggrecan G3 domain exert two separable functions in glycosaminoglycan modification and product secretion
The Journal of Biological Chemistry
(2002) - et al.
Age-related changes in the structure of the proteoglycan subunits from human articular cartilage
The Journal of Biological Chemistry
(1980) - et al.
Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4)
The Journal of Biological Chemistry
(2000) - et al.
Studies on the interaction of newly secreted proteoglycan subunits with hyaluronate in human articular cartilage
Biochimica et Biophysica Acta
(1990) - et al.
Link protein can retard the degradation of hyaluronan in proteoglycan aggregates
Osteoarthritis and Cartilage
(2006)
Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix metalloproteinase-13
The Journal of Biological Chemistry
SLRP interaction can protect collagen fibrils from cleavage by collagenases
Matrix Biology
The characterization of versican and its message in human articular cartilage and intervertebral disc
Journal of Orthopaedic Research
The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor
The Journal of Biological Chemistry
Differential ability of heparan sulfate proteoglycans to assemble the fibroblast growth factor receptor complex in situ
The FASEB Journal
Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia
American Journal of Human Genetics
Phenotypic modulation of newly synthesized proteoglycans in human cartilage and chondrocytes
Osteoarthritis and Cartilage
Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments
Osteoarthritis and Cartilage
Perlecan in late stages of osteoarthritis of the human knee joint
Osteoarthritis and Cartilage
Elucidation of IL-1/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression
Osteoarthritis and Cartilage
Effects of transforming growth factor-beta on aggrecanase production and proteoglycan degradation by human chondrocytes in vitro
Osteoarthritis and Cartilage
Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte
Osteoarthritis and Cartilage
Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis
Osteoarthritis and Cartilage
Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation
Osteoarthritis and Cartilage
IGF and IGF-binding protein system in the synovial fluid of osteoarthritic and rheumatoid arthritic patients
Osteoarthritis and Cartilage
Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage
The American Journal of Pathology
Hepatocyte growth factor in human osteoarthritic cartilage
Osteoarthritis and Cartilage
Regulation of osteoblast, chondrocyte, and osteoclast functions by fibroblast growth factor (FGF)-18 in comparison with FGF-2 and FGF-10
The Journal of Biological Chemistry
Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis
Osteoarthritis and Cartilage
Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family
The Journal of Biological Chemistry
Human cartilage glycoprotein 39 (HC gp-39) mRNA expression in adult and fetal chondrocytes, osteoblasts and osteocytes by in-situ hybridization
Osteoarthritis and Cartilage
YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes
Biochemical and Biophysical Research Communications
HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions
Osteoarthritis and Cartilage
Chemical composition of human femoral and head cartilage: influence of topographical position and fibrillation
Annals of the Rheumatic Diseases
Morphology of cartilage
ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis
Arthritis Research & Therapy
Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders
Arthritis and Rheumatism
The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes: A role in osteoarthritis
The Journal of Clinical Investigation
Folding defects in fibrillar collagens
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy)
Proceedings of the National Academy of Sciences of the United States of America
Clinical correlations of osteoarthritis associated with a single-base mutation (arginine519 to cysteine) in type II procollagen gene. A newly defined pathogenesis
Arthritis and Rheumatism
Articular cartilage collagen: an irreplaceable framework?
European Cells & Materials
Collagens and cartilage matrix homeostasis
Clinical Orthopaedics and Related Research
The complete primary structure of two distinct forms of human alpha 1 (IX) collagen chains
European Journal of Biochemistry
Genetic risk factors for lumbar disc disease
Annals of Medicine
Immunohistochemical analysis of type-X-collagen expression in osteoarthritis of the hip joint
Journal of Orthopaedic Research
The molecular genetics of inherited cartilage disease
Osteoarthritis and Cartilage
Genetic aspects of osteoarthritis
Seminars in Arthritis and Rheumatism
Studies on the G3 domain of aggrecan from human cartilage
Annals of the New York Academy of Sciences
Ageing and the aggregating proteoglycans of human articular cartilage
Clinical Science (London, England)
Cited by (401)
Pharmacological activation of the Nrf2 pathway by Taxifolin remodels articular cartilage microenvironment for the therapy of Osteoarthritis
2023, International ImmunopharmacologyHip adduction angle during wider step-width gait affects hip adduction moment impulse
2023, Gait and PostureApplication of magnetic particle imaging to evaluate nanoparticle fate in rodent joints
2023, Journal of Controlled ReleaseComparative Study of the Pain, Function, and Biomarkers of Joint Disease in the Transition to Adulthood in Individuals with and Without Cerebral Palsy
2024, American Journal of Physical Medicine and RehabilitationEfficacy and Safety of High Density LED Irradiation Therapy for Patients With Hand Osteoarthritis: A Single-Center Clinical Study
2024, Annals of Rehabilitation Medicine