Osteoarthritic cartilage contains increased calcium, magnesium and phosphorus.

Using plasma emission spectroscopy, we measured the calcium (Ca), phosphorus (P), magnesium (Mg), and sulphur (S) concentration in femoral head cartilage from 7 patients with osteoarthritis (OA) and 22 normal patients. We found that in OA cartilage Ca = 271.9 +/- 32.7 mmol/kg dry weight compared to Ca = 113.2 +/- 12.6 mmol/kg dry weight in normal controls. The Ca:P molar ratio in OA cartilage was 1.93 compared to Ca:P = 2.27 in normals, and Ca:P = 1.67 in apatite crystals. We conclude that OA cartilage has a greater binding capacity for Ca, Mg, and P than does normal cartilage. Apatite crystals, if present, comprise maximally 0.4% wet weight of OA cartilage.

The role of cytokines in arthritic diseases: in vitro and in vivo measurements of cartilage degradation.

The injection of partially purified porcine synovial catabolin/IL-1 alpha intra-articularly in rabbits resulted in a 50% loss of glycosaminoglycan (GAG) after 3 days. An increase in the synovial fluid content of GAG was found, and 35SO4 incorporation into proteoglycan was inhibited. Measurements were also made of the GAG loss from articular cartilage into the synovial fluid in human rheumatoid (RA) and osteoarthritic (OA) patients. Very high levels of GAG content in the synovial fluid was found, and calculations were made of the half-life of the cartilage proteoglycan during the active phases of the disease. Estimation of the synovial fluid GAG is believed to be a simple and quantitative method for monitoring the effectiveness of cartilage-"sparing" anti-arthritic drugs.

Polypeptide proteinase inhibitor from human articular cartilage.

A polypeptide proteinase inhibitor from human articular cartilage has been purified to homogeneity by stepwise Sephadex G-75, heparin-Sepharose and octyl-Sepharose affinity chromatography. The inhibitor is strongly cationic (pI greater than or equal to 10.5) and consists of two non-identical polypeptides associated by means of electrostatic and/or hydrophobic interactions. Amino acid analysis of the aggregate confirmed that the polypeptide was rich in basic, and hydrophobic amino acids and contained only one disulphide bridge. Sedimentation equilibrium studies showed that the aggregate had MW congruent to 7000 which could be dissociated into two polypeptides each of MW congruent to 3500. While the subunits were primarily serine proteinase inhibitors the aggregate form could also inhibit bacterial collagenase and pepsin but not thermolysin nor the cysteine proteinases, ficin or bromelain. Binding of 125I-labelled human cartilage inhibitor to heparin, keratan sulphate and proteoglycan subunit was demonstrated using gel exclusion chromatography but no interaction was detected with chondroitin 6-sulphate or hyaluronic acid. Binding of cartilage inhibitor subunits to link proteins was also shown by polyacrylamide electrophoresis. These data suggest that the human cartilage inhibitor may be localised at specific sites on the proteoglycan complex where it would be ideally placed to attenuate degradation by matrix proteinases or constitute part of an enzyme-inhibitor complex.

[Pharmacologic evaluation of the feasibility of cartilage therapy in degenerative joint diseases (arthroses)]. / Pharmakologische Beurteilung von Möglichkeiten einer Knorpelschutztherapie bei degenerativen Gelenkerkrankungen (Arthrosen).

Due to their pharmacological properties most antiphlogistic/antirheumatic drugs are successfully used for treatment of inflammatory rheumatic diseases, but they are not able to counteract cartilage degeneration in osteoarthrosis. For specific therapy of osteoarthrosis only those drugs are suitable, which are able to inhibit enzymatic breakdown of articular cartilage, stimulate anabolic processes in cartilage, and to enhance the supply of nutritional and energy substrates for the cartilage cells. In this respect drugs such as Arteparon, Rumalon, Dona 200-S, Glyvenol or Pentosan polysulfate are of interest. A great number of pharmacological experiments have shown, that certain chondroprotective agents exert pronounced anti-degenerative effects, which can be quantitatively demonstrated in laboratory animals within 3 to 4 months by macroscopical, radiological and histological methods. Additional biochemical and in-vitro studies have elucidated some interesting chondro-protective, chondro-stimulatory or chondro-nutritive properties of certain drugs. In agreement with our experimental results clinical experiences have proved the efficacy of chondro-protective agents. Due to the bradytrophia of human articular cartilage a chondro-protective therapy may be only effective in long-term applications, resulting in a significant reduction of the intensity and progression of the degenerative joint destruction.

Comparison of cartilage destruction between infectious and adjuvant arthritis.

The timing and molecular profile of cartilage destruction in Escherichia coli and Staphylococcus aureus infectious arthritis and killed Mycobacterium butyricum adjuvant arthritis are presented. Infectious arthritis was studied for 3 weeks; cartilage samples were analyzed at 2, 10, and 21 days. At 48 h postinfection, glycosaminoglycan content was reduced by 20% (p less than 0.05) in E. coli infected knees and by 42% (p less than 0.05) in tibial plateau cartilage of S. aureus infected knees. By the 3rd week of infection, glycosaminoglycan losses amounted to as much as 73% (p less than 0.005). In comparison, collagen losses were not significant prior to the 3rd week of infection, at which time 42% (p less than 0.05) was lost. Adjuvant arthritic tibial plateau cartilage was examined at 1, 3 and 12 weeks. Glycosaminoglycans decreased by 42% the 1st week, plateauing at 62% by the 3rd and 12th weeks. Collagen degradation began at 3 weeks (28% loss, p less than 0.10) and by the 12th week was reduced by 49% (p less than 0.005). Analysis of the individual species of glycosaminoglycan showed a parallel loss of chondroitin sulfate and keratan sulfate. Fractionation of glycosaminoglycans with respect to size produced no evidence of shortened chains in cartilage from infected joints. Hyaluronic acid losses were greatest when collagen was significantly decreased. The pattern by which chondroitin and keratan sulfates are lost demonstrates that a prominent feature of infectious and noninfectious inflammatory arthritis is a rapid loss of proteoglycan subunits that precedes collagen loss.

Some further effects of prednisolone and triamcinolone hexacetonide on experimental arthritis in rabbits.

Prolonged treatment of rabbits with an established bilaterally symmetrical experimental arthritis with prednisolone (0.5 mg/kg day) reduced both the swelling and the histopathological changes in the arthritic joints whereas short-term treatment suppressed only the swelling. Such prolonged treatment also suppressed both the humoral and cell-mediated immune responses measured systemically in these animals and the cell-mediated immune responsiveness of the synovium determined by lymphokine production by cultured explants. The results suggested that the suppressive effect of the drug on the arthritis was related to the inhibition of cell-mediated immune responsiveness. Prednisolone treatment also had deleterious effect on cartilage proteoglycan metabolism determined both histologically and biochemically. Intra-articular administration of triamcinolone hexacetonide (three injections of 2 mg per joint at fortnightly intervals) also reduced the swelling and histopathological changes, although there was no effect on circulating antibody levels.

Biological properties and clinical application of propolis. VI. Investigation of the influence of ethanol extracts of propolis (EEP) on cartilaginous tissue regeneration.

Dressing of artificially formed losses of the cartilaginous tissue with the preparation containing ethanol extract of propolis (EEP) caused acceleration of regenerating processes in the lesioned cartilage. EEP inserted into the joint is well tolerated.

Apatite deposition disease. A new arthropathy.

A method for identifying particles of crystalline calcium hydroxyapatite in synovial fluids and biopsy material has been developed with high-resolution scanning electron microscopy and an energy-dispersive micro-analytical system. Particles of hydroxyapatite were identified in the joints of six patients diagnosed as having osteoarthritis, three of whom had acute inflammatory episodes with effusions into the joints. Apatite was not identified in joints affected by rheumatoid arthritis and other types of arthropathy. Animal studies showed that hydroxyapatic crystals can cause an acute inflammatory reaction, and this has been confirmed by experimental studies in man. It is suggested that a third type of crystal-deposition disease should be recognised--namely, calcium-hydroxyapatite crystal-deposition disease.