GLYCOSAMINOGLYCAN METABOLISM AND CYTOKINE RELEASE IN NORMAL AND OTOSCLEROTIC HUMAN BONE-CELLS INTERLEUKIN-1 TREATED

Glycosaminoglycans (GAGs), normal components of the extracellular matr ix (ECM), and the glycosidases, that degrade them, play a key role in the bone remodelling process. The effects of interleukin-1 alpha (IL-1 alpha) on GAG metabolism in normal and otosclerotic human bone cells as well as its capacity to modulate IL-1 alpha, IL-1 beta and IL-6 sec retion in both populations was analyzed. The amount of radiolabeled GA Gs was lower in otosclerotic than in normal bone cells. IL-1 alpha red uced newly synthesized cellular and extracellular GAGs in normal cells , but only those of the cellular compartment in otosclerotic bone cell s. It depressed heparan sulphate (HS) more in normal cells and chondro itin sulphate (CS) more in otosclerotic bone cells. The HA/total sulph ated GAG ratio was shifted in favour of the latter in otosclerotic cel ls, whereas the opposite effect was seen after IL-1 alpha treatment. T here was little difference in the beta-D-glucuronidase levels of the n ormal and pathological cells, while beta-N-acetyl-D-glucosaminidase wa s significantly increased in otosclerotic bone cells. As the activity of neither enzyme was modified by treatment with IL-1 alpha, the cytok ine seems to exert its influences on GAG synthesis rather than on the degradation process. IL-1 alpha, IL-1 beta and IL-6 secretion was mark edly higher in otosclerotic cells. IL-1 alpha modulated the secretion of each interleukin differently, thus resulting in a cytokine cascade that may act in autocrine/paracrine manner on target cells. The author s suggest that changes in the cytokine network may have a specific, ye t still unknown, role during normal and pathological osteogenesis.