Disparate bone anabolic cues activate bone formation by regulating the rapid lysosomal degradation of sclerostin protein.

ABSTRACT: The downregulation of sclerostin in osteocytes mediates bone formation in response to mechanical cues and parathyroid hormone (PTH). To date, the regulation of sclerostin has been attributed exclusively to the transcriptional downregulation of the Sost gene hours after stimulation. Using mouse models and rodent cell lines, we describe the rapid, minute-scale post-translational degradation of sclerostin protein by the lysosome following mechanical load and PTH. We present a model, integrating both new and established mechanically and hormonally activated effectors into the regulated degradation of sclerostin by lysosomes. Using a mouse forelimb mechanical loading model, we find transient inhibition of lysosomal degradation or the upstream mechano-signaling pathway controlling scleros

SUBMITTER: Gould NR 

PROVIDER: S-EPMC8032393 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature