Oncostatin M induces upregulation of β-arrestin 2 and growth inhibition in osteosarcoma cells

Background: The objective of this study was to investigate the expression of β-arrestin 2 in G292 fibroblast-like phenotype osteosarcoma cells after stimulation with oncostatin M, a gp130-type multifunctional cytokine of the interleukin-6 family. Methods: The changes in β-arrestin 2 mRNA levels in G292 cells following staurosporine and oncostatin M treatments were analyzed by RT-PCR. The signal transduction pathways including MAP 44/42 and signal transducer and activator of transcription (STAT) were also evaluated by western blotting. Growth inhibition of tumor cells after treatment with oncostatin M was also assessed by tetrazolium (MTT) assay. Results: The level of β-arrestin 2 mRNA in these cells was upregulated in a time- and dose-dependent manner. Levels of β-arrestin 2 mRNA were increased 1.22- and 1.74-fold after 12 and 24 h of treatment with 10 ng/ml oncostatin M (P < 0.05), and 100 ng/ ml of oncostatin M induced even higher levels of β-arrestin 2 mRNA. Increased phosphorylation of MAP 44/42 and STAT3(Ser 727) were also noted, without alteration in the phosphorylation of STAT1(Ser 727), STAT3(Thr 705), STAT5(Tyr 694) or STAT6(Tyr 641). Growth inhibition of the tumor cells was also revealed by a 17.2% decrease in cell number after 24 h incubation. Conclusions: The data indicated that oncostatin M might reduce growth rate of osteosarcoma cells by upregulation of β-affestin 2 and the activation of MAP44/42 and STAT3(Ser 727). The findings provide useful information for elucidating the mechanism of oncostatin M-mediated growth inhibition in osteosarcoma cells.