EFFECT OF EXOGENOUS HYALURONAN AND HYALURONAN OLIGOSACCHARIDES ON HYALURONAN AND AGGRECAN SYNTHESIS AND CATABOLISM IN ADULT ARTICULAR-CARTILAGE EXPLANTS

The addition of hyaluronan to the culture medium of explant cultures o f articular cartilage was shown to suppress the synthesis of hyalurona n and aggrecan, the major proteoglycan present in cartilage, and resul ted in a greater proportion of the newly synthesized aggrecan and hyal uronan appearing in the culture medium. This effect of exogenous hyalu ronan on aggrecan and hyaluronan synthesis was concentration-dependent and reversible on removal of the glycosaminoglycan from the culture m edium. The addition of tetra- and hexasaccharides derived from Strepto myces sp. hyaluronidase digestion of hyaluronan to explant cultures of articular cartilage did not change the rate of synthesis of aggrecan or hyaluronan or their ultimate distribution between tissue and medium . However, the addition of tetra- and hexasaccharides of hyaluronan re sulted in a decrease in the rate of loss of hyaluronan from the tissue but not that of aggrecan, which remained the same as in control cultu res. This suppression of the rate of loss of hyaluronan was eliminated on removal of the hyaluronan oligosaccharides from the culture medium . Analysis of the hydrodynamic size of the newly synthesized hyalurona n indicated that the presence of hyaluronan tetra- and hexasaccharides brought about an accumulation of hyaluronan of intermediate molecular mass. Since no radiolabeled hyaluronan was detected in the culture me dium, it was concluded that the tetra- and hexasaccharides inhibited t he internalization and intracellular catabolism of hyaluronan by the c artilage explant cultures. Regardless of whether hyaluronan or tetra- and hexasaccharides of hyaluronan were added to the culture medium, ne wly synthesized hyaluronan underwent depolymerization at a rate consis tent with a mechanism involving oxygen-derived radicals. (C) 1995 Acad emic Press, Inc.