Macrophagic Sclerostin Loop2-ApoER2 Interaction Required by Sclerostin for Suppressing Inflammatory Responses

Background: Clinically, humanized anti-sclerostin antibody imposed cardiovascular events. Sclerostin demonstrated to protect cardiovascular system by inhibiting inflammatory responses, atherosclerosis and AA in SOSTki.ApoE-/- mice. The central residues of sclerostin form three loops. Sclerostin antibody targeted loop2 and loop3. In our published work, blockade of sclerostin antibody-sclerostin loop2 interaction attenuated antibody-induced aggravation of inflammatory responses, atherosclerosis and AA in ApoE-/- mice, whereas the cardiovascular protective effect of sclerostin was independent of loop3.