B4GALNT3 regulates glycosylation of sclerostin and bone mass.

ABSTRACT:

Background

Global sclerostin inhibition reduces fracture risk efficiently but has been associated with cardiovascular side effects. The strongest genetic signal for circulating sclerostin is in the B4GALNT3 gene region, but the causal gene is unknown. B4GALNT3 expresses the enzyme beta-1,4-N-acetylgalactosaminyltransferase 3 that transfers N-acetylgalactosamine onto N-acetylglucosaminebeta-benzyl on protein epitopes (LDN-glycosylation).

Methods

To determine if B4GALNT3 is the causal gene, B4galnt3^-/- mice were developed and serum levels of total sclerostin and LDN-glycosylated sclerostin were analysed and mechanistic studies were performed in osteoblast-like cells. Mendelian randomization was used to determine causal associations.

Findings

B4galnt3^-/-<

SUBMITTER: Moverare-Skrtic S 

PROVIDER: S-EPMC10102813 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature