salicylates and Cartilage-Diseases

Topics: Adrenal Cortex Hormones; Cartilage Diseases; Exercise Therapy; Humans; Indomethacin; Injections, Intra-Articular; Osteoarthritis; Phenylbutazone; Physical Therapy Modalities; Radiography; Rest; Salicylates; Spinal Diseases; Synovial Fluid; United States

Nitric oxide (NO) is thought to mediate most effects of interleukin-1 (IL-1) on cartilage. In vitro evidence includes the decreased synthesis of extracellular matrix components, the abnormal cell renewal, the decreased production of IL-1 receptor antagonist, the induction of apoptosis and the enhanced sensitivity of chondrocytes to oxidative stress. Studies in NOS2(-/-) mice or administration of NO synthase inhibitors in animal models of joint disorders have confirmed its potent pathophysiological role in cartilage. Using L-NMMA (1 mM), as a NO synthase inhibitor, and CuDips (10 microM), as a SOD mimetic, we provide evidence that the inhibitory potency of IL-1beta on proteoglycan synthesis and its stimulating effect on COX-2 activity depend both on NO and O2-* production. Peroxynitrite formation is further demonstrated by the occurrence of 3-nitrotyrosines in chondrocytes stimulated in vitro with 2.5 ng/ml IL-1 and in femoral condyles of rats injected locally with 1 microg IL-1. Preliminary data suggest that such contribution of reactive oxygen species is not shared in common by IL-17, another NO-producing cytokine. We conclude that superoxide is a key modulator of NO-mediated effects in chondrocyte stimulated with IL-1 and that a combined therapy with NO synthase inhibitors and antioxidants may be promising for a full cartilage protection.

Topics: Animals; Cartilage Diseases; Cartilage, Articular; Cells, Cultured; Chondrocytes; Depression, Chemical; Enzyme Inhibitors; Free Radical Scavengers; Humans; Interleukin-1; Interleukin-17; Male; Models, Animal; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Proteoglycans; Rats; Rats, Wistar; Salicylates

Topics: Ankle Joint; Arthritis, Rheumatoid; Cartilage Diseases; Cartilage, Articular; Chronic Disease; Foot Deformities, Acquired; Hallux Valgus; Humans; Joint Dislocations; Metatarsophalangeal Joint; Orthotic Devices; Physical Exertion; Salicylates; Shoes; Toes

Prostaglandins are found in increased concentrations in various arthritic joint fluids, and the E and F series have been shown to produce inflammation. Vane suggests that the effectiveness of aspirin is mediated by inhibition of synthesis or release of prostaglandins. In our studies PGE-1 intra-articularly produced the greatest amount of synovial and cartilage damage of the several PGs tested. Five knee intra-articular injections of 500 ng PGE-1 were given to 12 mature white New Zealand rabbits at 4 day intervals, with control solutions on the opposite sides. Four with intramuscular chloroquine at clinical levels and 4 controls. At 20 days histologic examination with H & E and safranin-O showed increased synovitis and abnormal cartilage in the controls and salicylate groups, normal cartilage in the chloroquine group. Whereas chloroquine's ability to stabilize cell membranes is protective in this experiment, salicylate's ability to prevent biosynthesis of prostaglandins is bypassed and therefore is not protective. Vane's hypothesis is supported by this study of PG induced experimental arthritis.

Topics: Animals; Cartilage Diseases; Cartilage, Articular; Chloroquine; Injections, Intra-Articular; Knee Joint; Rabbits; Salicylates; Staining and Labeling; Synovial Membrane

The major problem in osteoarthritis research today is our inability to promote effective cartilage regeneration in the presence of adult chondromalacia. Yet such regeneration is consistently present in acromegalics. The present study of experimentally damaged rabbit knee cartilage measures numbers of cells, mitoses, tritiated thymidine incorporation, DNA content, collagen presence under polarized light and sulfated protein polysaccharides histologically. Under growth hormone stimulation cell counts nearly double as compared to controls, TTI increases, DNA content triples or more. Matrix healing is evident histologically. The addition of salicylate has a mild additive effect on cell counts and on retention of matrix. The above data appear to be the first reported demonstration of these effects of growth hormone on experimentally damaged cartilage and may gain importance for clinical use when human growth hormone or substitutes for it become available.

Topics: Animals; Autoradiography; Bone and Bones; Cartilage Diseases; Cartilage, Articular; Cattle; Cell Count; Collagen; DNA; Growth Hormone; Joints; Knee Joint; Mitosis; Patella; Rabbits; Salicylates; Swine; Thymidine; Wound Healing