Effect of different biomaterials on the expression pattern of the transcription factor Ets2 in bone-like constructs.

Tissue engineering offers an exciting prospect for reconstructive surgery by replacing missing natural scaffolds with artificial ones. For optimal success the artificial scaffold should provide an environment closely resembling the natural tissue. Little is known about the direct influence of the scaffold on the expression of regulators of bone development, such as transcription factors. The aim of this study was to investigate the influence of the scaffold material on the expression of V-ets erythroblastosis virus E26 oncogene homolog 2 (avian) (Ets2), a key transcription factor in bone biology. Human primary bone precursor cells were seeded in three-dimensional constructs consisting of hydroxyapatite (HA) or poly (lactic-co-glycolic acid) (PLGA). Cells grown on tissue culture polystyrene dishes served as controls. After cultivation for up to 21 days the expression of Ets2 and other important bone-specific genes was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western Blotting. Ets2 mRNA showed significantly higher expression in controls than in bone-like constructs, and more Ets2 mRNA was expressed in cells grown in HA than in PLGA constructs. At protein level however, Ets2 expression was higher in constructs than in controls after prolonged culture. Our study showed for the first time a differential expression of Ets2 in tissue engineered bone constructs in vitro, demonstrating that scaffold chemistry has an influence on the expression of genes regulating osteogenesis.

The effect of nimesulide, a selective cyclooxygenase-2 inhibitor, on Ets-1 and Ets-2 expression in head and neck cancer cell lines.

BACKGROUND: The protooncogenes Ets-1 and Ets-2 are involved in carcinogenesis of different tumors. Nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, has antiproliferative effects on tumor cells. The question arises whether nimesulide influences Ets-1 and Ets-2 synthesis in head and neck tumors. METHODS: Expression of Ets-1 and Ets-2 was analyzed in tumor tissues by immunohistochemistry. The influence of nimesulide and an extracellular signal-regulated kinase (ERK) inhibitor on cell proliferation of two head and neck cancer cell lines and Ets-1 and Ets-2 expression was determined by automated cell counting and Western blotting, respectively. RESULTS: Immunohistochemistry showed a high expression of Ets-1 and Ets-2 in tumor tissues. In both cell lines, Ets-1 and Ets-2 expression were reduced after 24 and 48 hours by nimesulide. CONCLUSION: Both Ets-1 and Ets-2 are overexpressed in head and neck cancer specimens. Inhibition of Ets-1 and Ets-2 expression in head and neck cancer cell lines by nimesulide might explain the proapoptotic property of this COX-2 inhibitor.