Person:

Burstein, Deborah

Imaging of cartilage has traditionally been achieved indirectly with conventional radiography. Loss of joint space width, or 'joint space narrowing', is considered a surrogate marker for cartilage thinning. However, radiography is severely limited by its inability to visualize cartilage, the difficulty of ascertaining the optimum and reproducible positioning of the joint in serial assessments, and the difficulty of grading joint space narrowing visually. With the availability of advanced magnetic resonance imaging (MRI) scanners, new pulse sequences, and imaging techniques, direct visualization of cartilage has become possible. MRI enables visualization not only of cartilage but also of other important features of osteoarthritis simultaneously. 'Pre-radiographic' cartilage changes depicted by MRI can be measured reliably by a semiquantitative or quantitative approach. MRI enables accurate measurement of longitudinal changes in quantitative cartilage morphology in knee osteoarthritis. Moreover, compositional MRI allows imaging of 'pre-morphologic' changes (that is, visualization of subtle intrasubstance matrix changes before any obvious morphologic alterations occur). Detection of joint space narrowing on radiography seems outdated now that it is possible to directly visualize morphologic and pre-morphologic changes of cartilage by using conventional as well as complex MRI techniques.

In the present study we examined cartilage matrix repair following IL-1-induced matrix depletion. Previous data indicated that, in some cases, chondrocytes can synthesize macromolecules to establish a functional extracellular matrix in response to a matrix-damaging insult or when placed in a three-dimensional environment with inadequate matrix. However, the conditions under which such 'repair' can occur are not entirely clear. Prior studies have shown that chondrocytes in trypsin-depleted young bovine articular cartilage can replenish tissue glycosaminoglycan (GAG) and that the rate of replenishment is relatively uniform throughout the tissue, suggesting that all chondrocytes have similar capacity for repair. In the present study we used the characteristic heterogeneous distribution of matrix depletion in response to IL-1 exposure in order to investigate whether the severity of depletion influenced the rate of GAG replenishment. We used the delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) method to monitor the spatial and temporal evolution of tissue GAG concentration ([GAG]). For both mild (n=4) and moderate (n=10) IL-1-induced GAG depletion, we observed partial recovery of GAG (80% and 50% of baseline values, respectively) over a 3-week recovery period. During the first 2 weeks of recovery, [GAG] increased homogeneously at 10–15 mg/ml per week. However, during the third week the regions most severely depleted following IL-1 exposure showed negligible [GAG] accumulation, whereas those regions affected the least by IL-1 demonstrated the greatest accumulation. This finding could suggest that the most severely degraded regions do not recover fully, possibly because of more severe collagen damage; this possibility requires further examination.