1Emerging Frontiers in cartilage and chondrocyte biology
Section snippets
Will aggrecanase or collagenase inhibitors best protect against cartilage erosion in degenerative and rheumatic joint diseases?
The predominant collagen in adult articular cartilage is the fibrillar type II collagen, a homotrimer of α1(II) chains that assembles with collagen types IX and XI, extracellularly, to form heterofibrils. The type II collagen network gives cartilage its shape and tensile strength and provides a framework to resist the swelling pressure of aggrecan. Aggrecan swells because its many negatively charged glycosaminoglycan side chains attract counter ions, and consequently water, to create large
How do articular and growth plate cartilages differ?
Cartilage has two major roles in the human body, and chondrocytes adopt specific phenotypes for each of them. Mature articular cartilage is designed to last and function for an entire lifetime, so the resident cells have a slow turnover rate and normally display a stable phenotype [40], [41]. It is the articular cartilage that is compromised in adult joint diseases. By contrast, growth plate cartilage present in the developing skeletal anlagen forms a template for subsequent endochondral bone
Is it possible to repair cartilage?
One of the most vigorous areas of research relating to cartilage diseases in recent times has centred around strategies for cartilage repair (reviewed in [109]). The use of autologous chondrocytes to repair cartilage defects in humans was first described in 1994 by orthopaedic surgeons who harvested healthy chondrocytes from a non-weight-bearing region of the joint, expanded those cells in culture and then injected them as a suspension into a joint lesion beneath a periosteal flap that was
Perspectives
This chapter has reviewed important questions in cartilage biology. Our list of questions is subjective and incomplete, for example, cartilage interactions with subchondral bone, or the influence of biomechanical factors on chondrocyte physiology might be considered equally important. Nevertheless, answers to the questions we have discussed are critical for advancing our understanding of cartilage biology in health, OA and inflammatory arthritis. Answers to these questions will reveal
Acknowledgements
The authors acknowledge the support of the University of Melbourne, the Murdoch Children’s Research Institute and the Victorian Government’s Operational Infrastructure Support Program. A. J. Fosang is funded by the National Health and Medical Research Council (NHMRC) of Australia. F. Beier holds a Canada Research Chair and is supported by grants from the Canadian Institutes of Health Research (CIHR).
References (129)
- et al.
Association of the aggrecan keratan sulfate-rich region with collagen in bovine articular cartilage
Journal of Biological Chemistry
(1999) - et al.
Matrix degradation by chondrocytes cultured in alginate: IL-1 beta induces proteoglycan degradation and proMMP synthesis but does not result in collagen degradation
Osteoarthritis and Cartilage
(1998) - et al.
Aggrecan turnover in human articular cartilage: use of aspartic acid racemization as a marker of molecular age
Archives of Biochemistry and Biophysics
(1998) - et al.
Effect of collagen turnover on the accumulation of advanced glycation end products
Journal of Biological Chemistry
(2000) - et al.
The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor
Journal of Biological Chemistry
(2003) - et al.
The anticoagulant protein C pathway
FEBS Letters
(2005) - et al.
The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction
Journal of Biological and Chemistry
(1997) - et al.
Activation of human interstitial procollagenase through direct cleavage of the Leu83-Thr84 bond by mast cell chymase
Journal of Biological Chemistry
(1994) - et al.
The activation and physiological functions of the proprotein convertases
International Journal of Biochemistry Cellular Biology
(2008) - et al.
Characterization of a secreted form of human furin endoprotease
Biochemical Biophysics Research Communications
(1993)
Cell-surface processing of pro-ADAMTS9 by furin
Journal of Biological Chemistry
ADAMTS-4 (aggrecanase-1): N-Terminal activation mechanisms
Archives of Biochemistry and Biophysics
Characterization of proADAMTS5 processing by proprotein convertases
International Journal of Biochemistry and Cell Biology
Proprotein convertase activation of aggrecanases in cartilage in situ
Archives of Biochemistry and Biophysics
Lineage tracing using matrilin-1 gene expression reveals that articular chondrocytes exist as the joint interzone forms
Developmental Biology
A distinct cohort of progenitor cells participates in synovial joint and articular cartilage formation during mouse limb skeletogenesis
Developmental Biology
Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage
Bone and Mineral
Endoglin differentially regulates TGF-beta-induced Smad2/3 and Smad1/5 signalling and its expression correlates with extracellular matrix production and cellular differentiation state in human chondrocytes
Osteoarthritis Cartilage
The role of ERG (ets related gene) in cartilage development
Osteoarthritis Cartilage
Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis
Developmental Biology
Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine
Cell
DNA methylation in osteoarthritic chondrocytes: a new molecular target
Osteoarthritis and Cartilage
Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage
Osteoarthritis and Cartilage
Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis
Cell
Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems
American Journal of Human Genetics
Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase
Journal of Biological Chemistry
Nicotinamide Phosphoribosyltransferase s Essential for Interleukin-1{beta}-mediated dedifferentiation of articular chondrocytes via SIRT1 and extracellular Signal-regulated kinase (ERK) complex signaling
Journal of Biological Chemistry
The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells
FEBS Letters
MiR-140 is co-expressed with Wwp2-C transcript and activated by Sox9 to target Sp1 in maintaining the chondrocyte proliferation
FEBS Letters
MicroRNA-146a is linked to pain-related pathophysiology of osteoarthritis
Gene
Reversible collapse of rabbit ears after intravenous papain, and prevention of recovery by cortisone
Journal of Experimental Medicine
Aggrecan protects cartilage collagen from proteolytic cleavage
Journal of Biological Chemistry
Balance between swelling pressure and collagen tension in normal and degenerate cartilage
Nature
Cartilage of the hip joint. topographical variation of glycosaminoglycan content in normal and fibrillated tissue
Annals of the Rheumatic Diseases
Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay
Journal of Clinical Investigation
Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration
Journal of Clinical Investigation
Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair
Journal of Clinical Investigation
Expression and activity of ADAMTS-5 in synovium
European Journal of Biochemistry
Denaturation of type II collagen in articular cartilage in experimental murine arthritis. Evidence for collagen degradation in both reversible and irreversible cartilage damage
Jounal of Pathology.
Activation of procollagenases is a key control point in cartilage collagen degradation: interaction of serine and metalloproteinase pathways
Arthritis and Rheumatism
Activation of cartilage matrix metalloproteinases by activated protein C
Arthritis and Rheumatism
Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis
Arthritis and Rheumatism
Emerging roles of serine proteinases in tissue turnover in arthritis
Arthritis and Rheumatism
Matriptase activates stromelysin (MMP-3) and promotes tumor growth and angiogenesis
Cancer Sciences
Characterization of matriptase expression in normal human tissues
Journal of Histochemistry Cytochemistry
Mast cell responses in rheumatoid synovium. Association of the MCTC subset with matrix turnover and clinical progression
Arthritis and Rheumatism
Synovial mast cell responses during clinical improvement in early rheumatoid arthritis
Annals of the Rheumatic Diseases
Mast cells, cytokines, and metalloproteinases at the rheumatoid lesion: dual immunolocalisation studies
Annals of the Rheumatic Diseases
Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B
European Journal of Biochemistry
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2022, Journal of Clinical Orthopaedics and TraumaCitation Excerpt :There was no significant difference between the dGEMRIC values of the repair tissue between cultured MSCs and ACI (p > 0.05). The articular cartilage, being an avascular and aneural structure, has an extremely poor capacity to repair.1,17 Hence the synthesis of ECM after damage is poor and mostly consists of fibrocartilage-like scar tissue.