Figure 4.

Proposed exchange of sclerostin between skeletal and systemic compartments. Sclerostin, synthesized by osteocytes, is present within the bone microenvironment but also exchanges with the systemic circulation, where it is produced by several extraskeletal tissues, including the kidney. Whereas locally produced sclerostin is largely responsible for actions of sclerostin on bone, factors that influence circulating levels may also play a role, including variation in activity of B4GALNT3, which we propose protects sclerostin from degradation through generation of a terminal LacdiNAc.