Abstract: Sclerostin, encoded by the SOST gene, inhibits the Wnt pathway and, consequently, tends to decrease bone mass. Some polymorphisms of the SOST promoter have been associated with bone mineral density (BMD), but the molecular mechanisms involved are unknown. The aim of this study was to study the functional role of one polymorphism in vitro. We cloned the proximal promoter region of SOST gene, containing different alleles at the rs851054 SNP, in luciferase reporter vectors and transfected them into the cell lines HEK-293T, SAOS-2 and HOS-TE85. We did not find significant differences in the transcriptional activity of vectors with either the A or the G allele of the SNP. The co-transfection of vectors expressing RUNX2 and OSX markedly increased the transcriptional activity of the SOST promoter constructs (A allele, 2.5±0.9 fold, p<0.05; G allele, 1.9±0.8 fold, p<0.05), without significant differences between the rs851054 alleles. Moreover, no allele differences were detected in EMSAs. In conclusion, the DNA region upstream of the TSS of the SOST gene has a strong promoter activity that is enhanced by RUNX2 and OSX. Frequent allelic variants in this region have been associated with BMD, but the mechanisms involved remain to be elucidated because no functional differences between alleles were detected in vitro.

Autores/as

Descargar referencia