Glycosaminoglycan, collagen, and glycosidase changes in human osteoblasts treated with interleukin 1, and...

Normal bone homeostasis involves a balance between osteoblast and osteoclast action, regulated by hormones and cytokine stimuli. Hemodialysis patients appear to have increased production of interleukin-1 (IL-1), interleukin-6 (IL-6) and glycosaminoglycans (GAG) in serum. IL-1 plays a role in the synthesis, degradation and degree of sulphatation of ECM components such as glycosaminoglycans. Also, continuous changes in the ECM involve enzymes such as beta-N-acetyl-d-glucosaminidase (beta-NAG) and beta-d-glucuronidase (beta-GLU) which act on different GAG classes and collagen fibers. We examined the effects of IL-1alpha on ECM synthesis and the related enzymes in human uremic osteoblast cultures. We also measured the levels of IL-1beta, and IL-6 and alkaline phosphatase activity. In biopsies of uremic bone there was less ECM deposition than resorption associated with changes in osteoblast morphology. In vitro osteoblast proliferation was higher (P< or =0.01), and extracellular GAG lower (P< or =0.01) than in controls. The enzyme beta-NAG was high (P< or =0.05) but there were no noteworthy changes in beta-GLU. ELISA of the medium indicated spontaneous production of IL-1beta and IL-6, which significantly increased after IL-1alpha treatment compared to controls. IL-1alpha reduced alkaline phosphatase activity (P< or =0.01) in uremic osteoblast cultures. IL-1 acts on osteoblasts with decreases in GAG synthesis and alkaline phosphatase activity, while beta-NAG increases. This lead to a reduction in the organic component in ECM and its mineralization, and to changes in the regulation of cytokine activity by GAG. The enzymatic breakdown might be facilitated by metabolic acidosis and failed osteoblast differentiation; these factors could be correlated with different degrees of osteodystrophy.