Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration

Setton, Lori A.; Elliott, Dawn M.; Mow, Van C.

doi:10.1053/joca.1998.0170

Cited by 324 publications

(279 citation statements)

References 72 publications

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“…Compression and shear moduli are indicators of tissue mechanical function and depend on the abundance and integrity of ECM constituents Setton, et al, 1999;Zhu, et al, 1993). Whereas IL-1-stimulated tissue retains compression properties approximately 0-4% of the initial (t = 0) values by day 24, treatment with the non-selective metalloproteinase inhibitor was effective at preserving 15% and 42% of the initial equilibrium and dynamic compression moduli, respectively.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…Normal 3D deformations may serve as baseline data either in further analyses of cartilage damage [26] or in longitudinal studies of osteoarthritis in animal models [30]. Normal 3D deformations characterize (on a gross level) the deformation environment experienced by individual chondrocytes and thus may indicate that spatially-dependent deformations dominate chondrocyte mechanotransduction [3].…”

Section: Discussionmentioning

confidence: 99%

“…Water content distribution throughout the tissue is similar to that of collagen, accounting for more than 80% of the wet tissue weight at the surface and 65% in the deep zone. During the debilitating disease osteoarthritis, cartilage typically shows a decrease in collagen and proteoglycan content, and an increase in water content [30].…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous three-dimensional strain fields during unconfined cyclic compression in bovine articular cartilage explants

2005

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Articular cartilage provides critical load-bearing and tribological properties to the normal function of diarthrodial joints. The unique properties of cartilage, as well as heterogeneous deformations during mechanical compression, are due to the nonuniform microstructural organization of tissue components such as collagens and proteoglycans. A new cartilage deformation by tag registration (CDTR) technique has been developed by the authors to determine heterogeneous deformations in articular cartilage explants. The technique uses a combination of specialized MRI methods, a custom cyclic loading apparatus, and image processing software. The objective of this study was to use the CDTR technique to document strain patterns throughout the volume of normal bovine articular cartilage explants during cyclic unconfined compression at two physiologically-relevant applied normal stress levels (1.29 and 2.57 MPa). Despite simple uniaxial cyclic compressive loading with a flat, nonporous indenter, strain patterns were heterogeneous. Strains in the thickness direction (Eyy) were compressive, varied nonlinearly with depth from the articular surface from a maximum magnitude of 11% at the articular surface, and were comparable despite a 2-fold increase in applied normal stress. Strains perpendicular to the thickness direction (Exx and Ezz) were tensile, decreased linearly with depth from the articular surface from a maximum of 7%, and increased in magnitude 2.5-fold with a 2-fold increase in applied normal stress. Shear strains in the transverse plane (Ex:) were approximately zero while shear strains in the other two planes were much larger and increased in magnitude with depth from the articular surface, reaching maximum magnitudes of 2% at the articular cartilage-subchondral bone interface. In general, strain patterns indicated that cartilage osteochondral explants exhibited depth-dependent nonisotropic behavior during uniaxial cyclic loading. These results are useful in verifying constitutive formulations of articular cartilage during cyclic unconfined compression and in characterizing the micromechanical environment likely experienced by individual chondrocytes throughout the tissue volume.

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“…Furthermore, late-stage knee joints in experimentally immobilized chick embryos are lacking menisci (40). Importantly, injury or loss of the meniscus is known to initiate pathological changes in the articular cartilage of the knee (3,7,12,15,41,45), which are associated with alterations in the stress-strain environment in the joint (35,36,47). However, little is known of the sequence of biomechanical and biochemical events linking mechanical stress to inflammatory or degenerative changes of the meniscus and its interactions with articular cartilage relative to the onset and progression of arthritis.…”

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confidence: 99%

Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide

Shin¹,

Fermor²,

Weinberg³

et al. 2003

Journal of Applied Physiology

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. Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide. J Appl Physiol 95: 308-313, 2003. First published March 28, 2003 10.1152/ japplphysiol.00131.2003The meniscus is an intra-articular fibrocartilaginous structure that serves essential biomechanical roles in the knee. With injury or arthritis, the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likely contribute to the progression of joint disease. The goal of this study was to examine the influence of mechanical stress on matrix turnover in the meniscus in the presence of interleukin-1 (IL-1) and to determine the role of nitric oxide (NO) in these processes. Explants of porcine menisci were subjected to dynamic compressive stresses at 0.1 MPa for 24 h at 0.5 Hz with 1 ng/ml IL-1, and the synthesis of total protein, proteoglycan, and NO was measured. The effects of a nitric oxide synthase 2 (NOS2) inhibitor were determined. Dynamic compression significantly increased protein and proteoglycan synthesis by 68 and 58%, respectively, compared with uncompressed explants. This stimulatory effect of mechanical stress was prevented by the presence of IL-1 but was restored by specifically inhibiting NOS2. Release of proteoglycans into the medium was increased by IL-1 or mechanical compression and further enhanced by IL-1 and compression together. Stimulation of proteoglycan release in response to compression was dependent on NOS2 regardless of the presence of IL-1. These finding suggest that IL-1 may modulate the effects of mechanical stress on extracellular matrix turnover through a pathway that is dependent on NO.

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Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration

Abstract: These data and continued research using experimental models of OA provide a basis for our understanding of the pathogenesis and the time course of events in OA and will lead to the development of better procedures for disease intervention and treatment.

Cited by 324 publications

References 72 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

Heterogeneous three-dimensional strain fields during unconfined cyclic compression in bovine articular cartilage explants

Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide

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