LRP6 High Bone Mass Characterized in Two Generations Harboring a Unique Mutation of Low-Density Lipoprotein Receptor-Related Protein 6.

ABSTRACT: Osteoblast Wnt/β-catenin signaling conditions skeletal development and health. Bone formation is stimulated when on the osteoblast surface a Wnt binds to low-density lipoprotein receptor-related protein 5 (LRP5) or 6 (LRP6), in turn coupled to a frizzled receptor. Sclerostin and dickkopf1 inhibit osteogenesis if either links selectively to the first β-propeller of LRP5 or LRP6, thereby disassociating these cognate co-receptors from the frizzled receptor. Sixteen heterozygous mutations identified since 2002 within LRP5 and three heterozygous mutations identified since 2019 within LRP6 prevent this binding of sclerostin or dickkopf1 and account for the exceptionally rare, but highly instructive, autosomal dominant disorders called LRP5 and LRP6 high bone mass (HBM). Here

SUBMITTER: Whyte MP 

PROVIDER: S-EPMC10097642 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature