Genetics and Genomics of SOST: Functional Analysis of Variants and Genomic Regulation in Osteoblasts.

ABSTRACT: SOST encodes the sclerostin protein, which acts as a key extracellular inhibitor of the canonical Wnt pathway in bone, playing a crucial role in skeletal development and bone homeostasis. The objective of this work was to assess the functionality of two variants previously identified (the rare variant rs570754792 and the missense variant p.Val10Ile) and to investigate the physical interactors of the SOST proximal promoter region in bone cells. Through a promoter luciferase reporter assay we show that the minor allele of rs570754792, a variant located in the extended TATA box motif, displays a significant decrease in promoter activity. Likewise, through western blot studies of extracellular and intracellular sclerostin, we observe a reduced expression of the p.Val10Ile mutant

SUBMITTER: Martinez-Gil N 

PROVIDER: S-EPMC7825314 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature