Fig. 7. Schematic diagram depicting a molecular mechanism by which the CK2/USP4/SIRT1 signaling axis controls sclerostin expression in osteocytes.

CK2-induced USP4 phosphorylation mediates the deubiquitination of SIRT1 and stabilization of SIRT1. Upregulation of SIRT1 downregulates sclerostin expression in osteocytes and decreases a RANKL/OPG ratio, which decreases osteoclastogenesis and increases osteoblastogenesis simultaneously.