Disease-modifying Effects of Glucosamine on Interleukin-1β-treated Chondrosarcoma Cells (SW1353) Under Normoxic and Hypoxic Conditions

Background: With respect to interleukin (IL)-1β concentration, the disease-modifying effects of glucosamine HCl (GLN) on IL-1β-treated chondrocytes followed a dose-dependent manner and were traditionally conducted under normoxic conditions not generally encountered by chondrocytes in vivo. Purposes: To demonstrate the beneficial effects of GLN on IL-1β-induced matrix metalloproteinase (MMP) expression in chondrosarcoma cells in a dose-dependent manner, but at different concentration ranges of IL-1β; additionally, to determine how hypoxia affects GLN's beneficial effects after dose-dependent application. Methods: Under normoxic and hypoxic conditions, human chondrosarcoma cells (SW1353) induced by high and low IL-1β concentrations were respectively treated with low and high concentration ranges of GLN. mRNA and protein expression for MMPs and glucose transporter protein (GLUT)-1 were examined by reverse transcription-polymerase chain reaction and Western blot analysis. Results: High concentrations of GLN could reduce mRNA and protein expressions of MMPs induced by low concentration of IL-1β; whereas low concentrations of GLN could reduce the inflammatory response upregulated by high concentrations of IL-1β. The data might substantiate the beneficial effects in clinical application of lower plasma concentrations of GLN achievable by oral administration. Furthermore, the effects were compared under hypoxic conditions to mimic real conditions encountered in human cartilage under normoxia. Upregulation of HIF-1α protein levels under hypoxia was observed. The level of MMP protein expression induced by IL-1β was lower under hypoxic conditions. Instead, inhibition of MMPs by GLN appeared to be more apparent. Finally, GLUT-1 protein expression of SW1353 was upregulated under IL-1β and hypoxia treatment. Conclusion: Glucose transporter, most likely GLUT-1, inducible by HIF-1α, might play an important role in the therapeutic efficacy of a lower plasma concentration of GLN on osteoarthritis achievable by oral administration.