Fig. 4.

Loop2 and loop3 of sclerostin are key binding targets for sclerostin antibodies (Scl-abs). Both of them can mediate the bone formation suppression effect of sclerostin, while loop2 possesses a cardiovascular protective effect by decreasing inflammatory cytokines and chemokines such as IL-6, MCP-1, TNF-α, interferon-γ, et al., in VSMCs and macrophages. Scl-abs inhibit the functions of both loop2 and loop3, thus promoting bone formation but increasing cardiovascular risk. In contrast, the loop3-aptamer inhibits sclerostin’s bone suppression effect while preserving the cardioprotective effect of loop2