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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Cells, Cultured, Extracellular Signal-Regulated MAP Kinases, Humans, Immunosuppressive Agents, MAP Kinase Signaling System, Magnesium, Osteoblasts, Tacrolimus.
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Does immunosuppressant FK506 decrease the intracellular magnesium in the human osteoblast cell by inhibiting the ERK1/2 pathway? Context: Previous studies reported that FK506 influences bone mineralizing and hypomagnesemia, and also has immune modifying properties. This study examined whether or not the function of Mg2+ in bone metabolism plays a role in the loss of bone volume caused by immunosuppressants. The effects of the FK506 treatment on the intracellular magnesium and lactate dehydrogenase (LDH) activity were examined in cultured human osteoblasts (HOB) cells. The magnesium concentration was determined using microfluorescence techniques and atomic absorption spectrophotometry. Western blotting was used to measure the level of extracellular signal-regulated kinases 1/2 (ERK 1/2) activation. FK506 (0.1 microM) did not affect cell death in HOB cells after a 24 hour treatment but decreased the level of ERK 1/2 activation. In HOB cells, the mean [Mg2+]i after exposure to a 1 mM extracellular Mg2+ ([Mg2+]o) buffer was 0.53+/-0.01 mM (n=25). Exposure to 100 nM FK506 produced a significant decrease in [Mg2+]i (0.41+/-0.01 mM). The ERK inhibitor (PD98059) and FK506 produced similar effects but they were not cumulative.
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This study examined the role of ERK1/2 activation on the regulation of magnesium in HOB. These results suggest that the inhibition of ERK phosphorylation is an essential intermediate in the effects of FK506 on magnesium. Overall, FK506 causes bone disorders partly by decreasing [Mg2+]i accompanied by the inhibition of ERK 1/2. Final Decision: yes