Objective. The adduction moment at the knee during gait is the primary determinant of medial-tolateral load distribution. If the adduction moment contributes to progression of osteoarthritis (OA), then patients with advanced medial tibiofemoral OA should have higher adduction moments. The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age, sex, and pain level, and to examine the correlation of serum hyaluronan (HA) level with disease severity and with the adduction moment in a subset of patients.Methods. Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation. Disease severity was assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In a subset of 23 patients with available sera, HA was quantified by sandwich enzyme-linked immunosorbent assay. Pearson correlations, a random effects model, and multivariate regression models were used.Results. The adduction moment correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60, respectively), and with joint space width in the left and right knees (r = -0.45 and r = -0.47,

PRP isolated from autologous blood may be useful as a source of anabolic growth factors for stimulating chondrocytes to engineer cartilage tissue.

We have developed an enzyme-linked immunosorbent-inhibition assay which makes use of a moinoclonal antibody specific for keratan sulfate to quaintify keratan sulfate present as single chains in adult hurnan serum. In adults hospitalized with conditions not thought to affect the turnover of keratan sulfate-contairiing tissues, the serum levels varied from individual to individual (53-1,009 ng/ml) but did not show significant differences with respect to age, sex, or disease category. There were no significant differences between the serum levels of adult hospitalized patients and those of nonhospitalized normal adults. In contrast, the concentration of keratan sulfate in the sera of children aged 5-12 was significantly higher. No keratan sulfate was detected in the sera of 3 adult patients with macular corneal dystrophy, an inherited disorder of the cornea. This may indicate that individuals with macular corneal dystrophy have no keratan sulfate-containing proteoglycans in their cartilage. Adult patients with osteoarthritis have significantly higher concentrations of circulating keratan sulfate. This suggests that the assay could prove valuable in monitoring increased cartilage catabolism in joint diseases.The majority of proteoglycans (PGs) in cartilage are large molecular weight macromolecules that endow cartilage with its ability to undergo reversible deformation (1). These complex carbohydrates consist of a core protein ( M , = 25&380 x lo3) to which glycosaminoglycans (GAGS) and both 0-and N-linked oligosaccharides are covalently attached (1). In humans and many other species, there are over 100 chondroitin sulfate (CS) and keratan sulfate (KS) GAG side chains in a single PG monomer.The rate at which cartilage PGs turn over ( 2 4 ) and the mechanisms involved in the degradation of PGs in normal and pathologic cartilage (1 3-7) remain in question. There have been numerous reports of both anabolic and catabolic alterations in cartilage in diseases such as osteoarthritis (OA), rheumatoid arthritis, disc degeneration, and other diseases in which these tissues are affected (8-10). The absence of significant amounts of partially degraded PGs in normal cartilage matrix (1 1) suggests that individual PG molecules normally are rapidly degraded into smaller

Platelet-rich plasma was effective in stimulating cell proliferation and extracellular matrix metabolism. The response to platelet-rich plasma was greater in the case of anulus fibrosus cells than of nucleuspulposus cells. The local administration of platelet-rich plasma might stimulate intervertebral disc repair. In addition, given the risks of using animal serum for tissue engineering, autologous blood may gain favor as a source of growth factors and serum supplements needed for stimulating cells to engineer intervertebral disc tissues.

Bone, synovium, and articular cartilage all appear to be involved in the state of hypermetabolism that develops in unstable joints. Furthermore, the rate of bone resorption increases markedly in the early stages of this OA model and is likely to contribute to cartilage breakdown. Since calcitonin reduced the severity of OA changes, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury.

Objective. To compare synovial fluid (SF) levels of oncostatin M (OSM), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to determine which correlate best with SF levels of antigenic keratan sulfate (Ag KS), a marker of aggrecan catabolism, and pyridinium crosslinks, markers of the degradation of mature collagen molecules. Methods. SF was drawn from the knee joints of patients with RA (n 31) or OA (n 31). Levels of Ag KS, D-pyridinoline (D-Pyr), pyridinoline (Pyr), OSM, TNF, and IL-6 were measured by enzyme-linked im-munosorbent assay. Results. RA patients had higher median SF levels of OSM, TNF, IL-6, and Pyr, but a lower median level of D-Pyr, than OA patients. In both groups, IL-6 levels correlated positively with those of OSM and TNF. However, the correlation between levels of OSM and TNF was only significant in the RA group. Ag KS and Pyr levels correlated positively in RA but not in OA. The correlation between TNF and Ag KS was positive in RA and negative in OA. Further, in RA, OSM and IL-6 levels correlated strongly with Pyr and Ag KS levels but not with D-Pyr levels, while there were no strong correlations in OA for OSM or IL-6 levels with Pyr, Ag Ks, or D-Pyr levels. Conclusion. This in vivo study suggests that TNF and other proinflammatory cytokines are involved in the up-regulation of the coordinated degradation of cartilage aggrecan and collagen in RA. Further, OSM may act synergistically with other proinflamma-tory cytokines in up-regulating the production of me-talloproteinases by chondrocytes in rheumatoid joints. Fibril-forming collagens (types I-III, V, and XI) are the most abundant collagenous components of joint structures, where they form a meshwork of crosslinked fibrils that give the tissues most of their tensile strength (1). The 2 major forms of mature crosslinking residues found in polymers of fibrillar collagen are hydroxyly-sylpyridinoline, also termed pyridinoline (Pyr) and ly-sylpyridinoline, also referred to as deoxypyridinoline (D-Pyr) (2). Bone collagen is the primary repository of D-Pyr, while collagen from cartilage, meniscus, tendon, and joint capsule is rich in Pyr (2,3). In articular cartilage, crosslinked collagenous fibrils (types II, IX, and XI) also contribute indirectly to the resilience and compressive stiffness of the tissue by entrapping in an underhydrated form viscoelastic aggre-can molecules bearing numerous anionic chondroitin sulfate and keratan sulfate (KS) side chains (4,5). The mechanisms that regulate the normal turnover of these key functional elements and their degradation in arthrit-ides are still poorly understood. In recent years, the quantification of "molecular markers of joint metabo-Supported by the fonds de développement scientifique of the Université Catholique de Louvain, fund 3.4597.98 for Medical Scientific Research (Belgium), and grants AG-04736 and AR-39239 from the NIH, Bethesda, MD.

Plasma levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), measured by enzyme‐linked immunosorbent assay, were compared with levels in a healthy, age‐matched non‐arthritic control group, in a retrospective study. Compared with the controls, the mean level of plasma HA was sevenfold higher in the RA group and twofold higher in the OA group. There was no statistically significant correlation between HA levels and 7 other clinical and biochemical parameters in patients with RA. In the OA group, however, plasma HA levels were found to correlate with an objective functional capacity score and with an articular index based on the total amount of cartilage in involved joints. In a retrospective longitudinal study of 6 patients with RA, plasma levels of HA did not show a significant correlation with plasma levels of elastase or with the erythrocyte sedimentation rate. These data support in part the contention that plasma HA may be unique as a marker, in that it may be a reflection of synovial involvement and inflammation, rather than only of inflammation, in arthritis.

Because CT delivered as a nasal spray markedly reduced the severity of most OA changes, both at the histological and biochemical level, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury, and as well as for dogs who spontaneously rupture their ACL.