Use of chondroitin mono- and di-sulfates for preservation and regeneration of cartilage, useful for treating osteoarthritis, increase production of aggrecans

摘要

Use of chondroitins (I) sulfated at positions 2, 4, 6 and/or both 2,6 to produce a composition that acts as a preservation and regeneration factor in cartilage. ACTIVITY : Osteopathic; Antiarthritic. MECHANISM OF ACTION : (I) increase production of aggrecans (especially they increase synthesis of longer filaments of hyaluronan and of hyaluronic acid, and inhibit enzymes such as elastase, aggrecanase and cathepsin B); stimulate both production and aggregation of proteoglycans (PG) and also reverse disaggregation induced by interleukin-1 (IL-1), without modifying the phenotype of chondrocytes, which still show stable expression of type II collagen. The newly synthesized PG accumulate in the intracellular space, so preserve the physico-mechanical properties of cartilage. Commercial chondroitin sulfate (CS) was added to a culture of chondrocytes, in medium containing 35S-sulfate. In absence of CS, the mean incorporation of sulfate into PG (expressed as disintegrations per minute x 10-4 per 10 mg DNA) was 2.19 for medium and 1.23 for cells (36% in cells), but in presence of 100 mg/ml CS the figures were 2.20 and 2.19 (50% in cells). Addition of IL-1beta to cultures without CS caused a significant reduction in the percentage incorporated into cells (onyl 6% at 20 ng/ml IL-1beta ) but this effect by reduced by CS (33% in cells in presence of 20 ng/ml IL-1beta and 100 mg/ml CS).