Topographical analysis of the structural, biochemical and dynamic biomechanical properties of cartilage in an ovine model of osteoarthritis

Appleyard, Richard; Burkhardt, Daniel; Ghosh, Peter; Read, Roger W.; Cake, Martin; Swain, Michael V.; Murrell, George A. C.

doi:10.1053/joca.2002.0867

Cited by 167 publications

(179 citation statements)

References 38 publications

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“…The aggrecanase-selective inhibitor delayed (by ~4 days) and reduced loss of the dynamic compression modulus, but did not substantially alter loss of the equilibrium compression or dynamic shear moduli. These data are consistent with previously published findings that the dynamic material properties of cartilage depend upon collagen content (Appleyard, et al, 2003). Recent work in our lab, however, also demonstrated significant correlations between aggrecan contents and the dynamic shear and compression properties in IL-1-stimulated cartilage (Palmer, et al, 2005), and the improved retention of explant aggrecan content by a non-selective metalloproteinase inhibitor observed here may contribute to protection of dynamic material properties.…”

Section: Discussionsupporting

confidence: 93%

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

et al. 2007

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Articular cartilage undergoes matrix degradation and loss of mechanical properties when stimulated with proinflammatory cytokines such as interleukin-1 (IL-1). Aggrecanases and matrix metalloproteinases (MMPs) are thought to be principal downstream effectors of cytokine-induced matrix catabolism, and aggrecanase-or MMP-selective inhibitors reduce or block matrix destruction in several model systems. The objective of this study was to use metalloproteinase inhibitors to perturb IL-1-induced matrix catabolism in bovine cartilage explants and examine their effects on changes in tissue compression and shear properties. Explanted tissue was stimulated with IL-1 for up to 24 days in the absence or presence of inhibitors which were aggrecanase-selective, MMP-selective, or non-selective. Analysis of conditioned media and explant digests revealed that aggrecanase-mediated aggrecanolysis was delayed to varying extents with all inhibitor treatments, but that aggrecan release persisted. Collagen degradation was abrogated by MMP-and non-selective inhibitors and reduced by the aggrecanase inhibitor. The inhibitors delayed but did not reduce loss of the equilibrium compression modulus, whereas the loss of dynamic compression and shear moduli was delayed and reduced. The data suggest that non-metalloproteinase mechanisms participate in IL-1-induced matrix degradation and loss of tissue material properties.

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Section: Discussionsupporting

confidence: 93%

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

et al. 2007

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“…The superficial zone in the peripheral region contained smaller, flatter chondrocytes and a thicker zone of larger-diameter tangential fibers, while the central region contained larger, rounder cells and a thinner tangential fiber zone. While not specific to local thickness variations or spatial variations in cartilage morphology, biological and mechanical properties have been related to specific regions of cartilage [32][33][34][35][36][37][38] . For healthy cartilage, it has been shown that highly loaded regions show increased thickness and enhanced mechanical properties, while infrequently loaded regions show cartilage with degraded properties, including fibrillation, relative to loaded regions, even in relatively young subjects 29 .…”

Section: Discussionmentioning

confidence: 99%

Gait Mechanics Influence Healthy Cartilage Morphology and Osteoarthritis of the Knee

Andriacchi

Koo

Scanlan

2009

Journal of Bone and Joint Surgery

404

366

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The response of healthy and diseased cartilage of the knee to the mechanics of walking is examined, with the goal of providing insight into the relationship between the kinematics and kinetics of the knee during walking and the maintenance of cartilage health. The combination of information from three-dimensional thickness models of cartilage derived from magnetic resonance imaging and the analysis of the interaction between load at the knee and kinematic changes during walking associated with loss of the anterior cruciate ligament demonstrated the importance of considering walking mechanics as an important factor in the initiation and progression of osteoarthritis. In particular, this material suggests that knee cartilage becomes conditioned to loading and to the large number of repetitive cycles of loading that occur during walking and that healthy cartilage homeostasis is maintained as long as there are no changes to the normal patterns of locomotion, the structure of the knee joint, or cartilage biology. Thus, there is the potential for a degenerative pathway to be initiated when a condition such as anterior cruciate ligament injury causes the repetitive loading during walking to shift to a new location. The sensitivity of cartilage to the kinematic changes is illustrated with the anterior cruciate ligament-deficient knee and the regional variations in cartilage morphology. The material presented here supports the conclusion that individual variations in the range of loading and kinematics at the knee during walking can have a profound influence on the initiation and progression of osteoarthritis of the knee.

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“…Water content was analyzed using previously described methods (20,21). Briefly, 56 cartilage explants were used for the determination of water content.…”

Section: Mechanical Injurymentioning

confidence: 99%

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

Otsuki¹,

Brinson²,

Creighton³

et al. 2008

Arthritis & Rheumatism

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Objective. Loss of glycosaminoglycan (GAG) is an early event in osteoarthritis. Recent findings showed increased cell death in arthritic cartilage and linkage with extracellular matrix degradation. The aim of this study was to analyze the direct effect of GAG loss on chondrocyte survival and cell death following mechanical injury.Methods. In full-thickness cartilage explants from porcine knee joints, GAG was depleted by digestion with chondroitinase ABC. Explants were subjected to single-impact mechanical injury. Cell viability and the types of cell death were analyzed by Live/Dead cell assay, staining for active caspase 3, and sensitivity to caspase inhibitor.Results. GAG depletion did not directly lead to increased cell death. In chondroitinase ABC-treated explants, but not in control explants, mechanical injury caused an immediate reduction in cell viability (from 84.6% to 71.0%); the reduction was prominent in the superficial zone. This immediate cell death was not inhibited by the pancaspase inhibitor Z-VAD-FMK, suggesting cell necrosis. During subsequent culture, viability in these explants decreased further, to 50.5% on day 3. The second wave of cell death was reduced by the addition of Z-VAD-FMK in chondroitinase ABC-treated explants and was also associated with activation of caspase 3, suggesting apoptotic mechanisms of cell death.Conclusion. These results indicate that GAG loss alone does not directly lead to chondrocyte death. In response to mechanical injury, there is an immediate induction of necrotic cell death that is seen only in GAG-depleted explants and primarily in the superficial zone. During subsequent culture, cell death spreads via apoptotic mechanisms.

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Topographical analysis of the structural, biochemical and dynamic biomechanical properties of cartilage in an ovine model of osteoarthritis

Cited by 167 publications

References 38 publications

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced cartilage degradation and loss of mechanical properties

Gait Mechanics Influence Healthy Cartilage Morphology and Osteoarthritis of the Knee

The effect of glycosaminoglycan loss on chondrocyte viability: A study on porcine cartilage explants

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