Investigations of the Composition-Function Relationships in Normal, Degraded, and Engineered Articular Cartilage Using Epic-Microcomputed Tomography

Articular cartilage provides a low-friction surface during normal joint motion and distributes forces to the underlying bone. The extracellular matrix composition (ECM) of healthy cartilage has previously been shown to be an excellent predictor of its mechanical properties. Changes in ECM composition and loss of mechanical function are known to occur with degenerative conditions such as osteoarthritis. Identifying differences in the composition-function relationships of articular cartilage under different anabolic, catabolic, and homeostatic conditions may therefore be a useful approach for identifying factors (e.g. ECM content, distribution, and structure) which are critical to mechanical function. In addition, diagnostic tools capable of monitoring changes in the articular cartilage ECM may increase our understanding of the effects of ECM changes on composition-functions relationships.

The goals of this work were to investigate composition-function relationships in healthy, degraded, and engineered articular cartilage and to develop a µCT-based approach to analyze changes in matrix composition and morphology in articular cartilage. In healthy cartilage explants, compressive and shear properties were dependent on both sGAG and collagen content. In contrast, the compressive properties of IL-1-stimulated cartilage were dependent on sGAG but not collagen content. To assess changes in sGAG content, EPIC-µCT, a 3D contrast-enhanced microcomputed tomography technique was developed. EPIC-µCT attenuation was found to be an excellent predictor of sGAG content in IL-1-stimulated cartilage explants and engineered cartilage. In addition, analytical approaches were developed to use EPIC-µCT for the in situ analysis of cartilage morphology. EPIC-µCT was also used to analyze spatial differences in sGAG accumulation in bilayer engineered cartilage for comparison with the local strain profile. This work underscores the significance of ECM composition and structure in regulating cartilage mechanical properties and validates the use of EPIC-µCT as a diagnostic for monitoring sGAG content and potentially for assessing mechanical function in models of degeneration and regeneration.

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Year

Entry

2003

Ng L, Grodzinsky AJ, Patwari P, Sandy J, Plaas A, Ortiz C. Individual cartilage aggrecan macromolecules and their constituent glycosaminoglycans visualized via atomic force microscopy. J Struct Biol. September 2003;143(3):242-257.

2002

Wang CC-B, Guo XE, Sun D, Mow VC, Ateshian GA, Hung CT. The functional environment of chondrocytes within cartilage subjected to compressive loading: a theoretical and experimental approach. Biorheology. 2002;39(1-2):11-25.

1994

Guilak F, Meyer BC, Ratcliffe A, Mow VC. The effects of matrix compression on proteoglycan metabolism in articular cartilage explants. Osteoarthritis Cartilage. June 1994;2(2):91-101.

1979

Maroudas A. Physicochemical properties of articular cartilage. In: Freeman MAR, ed. Adult Articular Cartilage. 2nd ed. Kent, England: Pitman Medical; 1979:215-290.

2001

Williamson AK, Chen AC, Sah RL. Compressive properties and function—composition relationships of developing bovine articular cartilage. J Orthop Res. November 2001;19(6):1113-1121.