Co-deletion of Lrp5 and Lrp6 in the skeleton severely diminishes bone gain from sclerostin antibody administration.

ABSTRACT: The cysteine knot protein sclerostin is an osteocyte-derived secreted inhibitor of the Wnt co-receptors LRP5 and LRP6. LRP5 plays a dominant role in bone homeostasis, but we previously reported that Sost/sclerostin suppression significantly increased osteogenesis regardless of Lrp5 presence or absence. Those observations suggested that the bone forming effects of sclerostin inhibition can occur through Lrp6 (when Lrp5 is suppressed), or through other yet undiscovered mechanisms independent of Lrp5/6. To distinguish between these two possibilities, we generated mice with compound deletion of Lrp5 and Lrp6 selectively in bone, and treated them with sclerostin monoclonal antibody (Scl-mAb). All mice were homozygous flox for both Lrp5 and Lrp6 (Lrp5^f/f; Lrp6^f/f), and vari

SUBMITTER: Lim KE 

PROVIDER: S-EPMC7770084 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature