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Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage.

ABSTRACT: A biomechanical failure of the collagen network is postulated in many hypotheses of the development of osteoarthritis with advancing age. Here we investigate the accumulation of non-enzymatic glycation (NEG) products in healthy human articular cartilage, its relation to tissue remodelling and its role in tissue stiffening. Pentosidine levels were low up to age 20 years, and increased linearly after this age. This indicates extensive tissue remodelling at young age, and slow turnover of collagen after maturity has been reached. The slow remodelling is supported by the finding that enzymatic modifications of collagen (hydroxylysine, hydroxylysylpyridinoline, and lysylpyridinoline) were not related to age. The high remodelling is supported by levels of the crosslink lysylpyridinoline (LP) as a function of distance from the articular surface. LP was highest at the surface in mature cartilage (>20 years), whereas in young cartilage (<10 years) the opposite was seen; highest levels were close to the bone. LP levels in cartilage sections at age 14 years are high at the surface and close to the bone, but they are low in the middle region. This indicates that maturation of cartilage in the second decade of life starts in the upper half of the tissue, and occurs last in the tissue close to the bone. The effect of NEG products on instantaneous deformation of cartilage was investigated as a functional of topographical variations in pentosidine levels in vivo and in relation to in vitro induced NEG. Consistently, higher pentosidine levels were associated with a stiffer collagen network. A stiffer and more crosslinked collagen network may become more brittle and more prone to fatigue.

SUBMITTER: Bank RA

PROVIDER: S-EPMC1219146 | biostudies-other | 1998 Feb

REPOSITORIES: biostudies-other

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Project description:Osteoarthrosis is a debilitating disease affecting millions, yet engineering materials for cartilage regeneration has proven difficult because of the complex microstructure of this tissue. Articular cartilage, like many biological tissues, produces a time-dependent response to mechanical load that is critical to cell's physiological function in part due to solid and fluid phase interactions and property variations across multiple length scales. Recreating the time-dependent strain and fluid flow may be critical for successfully engineering replacement tissues but thus far has largely been neglected. Here, microindentation is used to accomplish three objectives: (1) quantify a material's time-dependent mechanical response, (2) map material properties at a cellular relevant length scale throughout zonal articular cartilage and (3) elucidate the underlying viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in articular cartilage. Untreated and trypsin-treated cartilage was sectioned perpendicular to the articular surface and indentation was used to evaluate properties throughout zonal cartilage on the cut surface. The experimental results demonstrated that within all cartilage zones, the mechanical response was well represented by a model assuming nonlinear biphasic behavior and did not follow conventional viscoelastic or linear poroelastic models. Additionally, 10% (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic material. The approach outlined here provides a method, applicable to many tissues and biomaterials, which reveals and quantifies the underlying causes of time-dependent deformation, elucidates key aspects of material structure and function, and that can be used to provide important inputs for computational models and targets for tissue engineering. STATEMENT OF SIGNIFICANCE:Elucidating the time-dependent mechanical behavior of cartilage, and other biological materials, is critical to adequately recapitulate native mechanosensory cues for cells. We used microindentation to map the time-dependent properties of untreated and trypsin treated cartilage throughout each cartilage zone. Unlike conventional approaches that combine viscoelastic and poroelastic behaviors into a single framework, we deconvoluted the mechanical response into separate contributions to time-dependent behavior. Poroelastic effects in all cartilage zones dominated the time-dependent behavior of articular cartilage, and a model that incorporates tension-compression nonlinearity best represented cartilage mechanical behavior. These results can be used to assess the success of regeneration and repair approaches, as design targets for tissue engineering, and for development of accurate computational models.

Project description:An exact understanding of the interplay between the articulating tissues of the knee joint in relation to the osteoarthritis (OA)-related degeneration process is of considerable interest. Therefore, the aim of the present study was to characterize the biomechanical properties of mildly and severely degenerated human knee joints, including their menisci and tibial and femoral articular cartilage (AC) surfaces. A spatial biomechanical mapping of the articulating knee joint surfaces of 12 mildly and 12 severely degenerated human cadaveric knee joints was assessed using a multiaxial mechanical testing machine. To do so, indentation stress relaxation tests were combined with thickness and water content measurements at the lateral and medial menisci and the AC of the tibial plateau and femoral condyles to calculate the instantaneous modulus (IM), relaxation modulus, relaxation percentage, maximum applied force during the indentation, and the water content. With progressing joint degeneration, we found an increase in the lateral and the medial meniscal instantaneous moduli (p < 0.02), relaxation moduli (p < 0.01), and maximum applied forces (p < 0.01), while for the underlying tibial AC, the IM (p = 0.01) and maximum applied force (p < 0.01) decreased only at the medial compartment. Degeneration had no influence on the relaxation percentage of the soft tissues. While the water content of the menisci did not change with progressing degeneration, the severely degenerated tibial AC contained more water (p < 0.04) compared to the mildly degenerated tibial cartilage. The results of this study indicate that degeneration-related (bio-)mechanical changes seem likely to be first detectable in the menisci before the articular knee joint cartilage is affected. Should these findings be further reinforced by structural and imaging analyses, the treatment and diagnostic paradigms of OA might be modified, focusing on the early detection of meniscal degeneration and its respective treatment, with the final aim to delay osteoarthritis onset.

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Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage.

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