Despite the compelling need mandated by the prevalence and morbidity of degenerative cartilage diseases, it is extremely difficult to study disease progression and therapeutic efficacy, either in vitro or in vivo (clinically). This is partly because no techniques have been available for nondestructively visualizing the distribution of functionally important macromolecules in living cartilage. Here we describe and validate a technique to image the glycosaminoglycan concentration (

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T2 and T1rho have potential to nondestructively detect cartilage degeneration. However, reports in the literature regarding their diagnostic interpretation are conflicting. In this study, T2 and T1rho were measured at 8.5 T in several systems: 1) Molecular suspensions of collagen and GAG (pure concentration effects): T2 and T1rho demonstrated an exponential decrease with increasing [collagen] and [GAG], with [collagen] dominating. T2 varied from 90 to 35 ms and T1rho from 125 to 55 ms in the range of 15-20% [collagen], indicating that hydration may be a more important contributor to these parameters than previously appreciated. 2) Macromolecules in an unoriented matrix (young bovine cartilage): In collagen matrices (trypsinized cartilage) T2 and T1rho values were consistent with the expected [collagen], suggesting that the matrix per se does not dominate relaxation effects. Collagen/GAG matrices (native cartilage) had 13% lower T2 and 17% lower T1rho than collagen matrices, consistent with their higher macromolecular concentration. Complex matrix degradation (interleukin-1 treatment) showed lower T2 and unchanged T1rho relative to native tissue, consistent with competing effects of concentration and molecular-level changes. In addition, the heterogeneous GAG profile in these samples was not reflected in T2 or T1rho. 3) Macromolecules in an oriented matrix (mature human tissue): An oriented collagen matrix (GAG-depleted human cartilage) showed T2 and T(1rho) variation with depth consistent with 16-21% [collagen] and/or fibril orientation (magic angle effects) seen on polarized light microscopy, suggesting that both hydration and structure comprise important factors. In other human cartilage regions, T2 and T1rho abnormalities were observed unrelated to GAG or collagen orientation differences, demonstrating that hydration and/or molecular-level changes are important. Overall, these studies illustrate that T2 and T1rho are sensitive to biologically meaningful changes in cartilage. However, contrary to some previous reports, they are not specific to any one inherent tissue parameter.

Joint pathology following DMM surgery in mice is associated with progressive mechanical allodynia. ADAMTS-5 null mice are resistant to DMM-induced OA-like lesions and to the associated mechanical allodynia.

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three-dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high-resolution digital imaging techniques such as magnetic resonance microimaging (MRI), micro-computed tomography (CT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three-dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies. Anat Rec (New Anat) 265:101-110, 2001.