Inhibition of sclerostin leads to activation of which signaling pathway that promotes osteoblast activity?

• A. Wnt pathway
• B. MAPK pathway
• C. Notch pathway
• D. PI3K/Akt pathway

Answer: (A)

Blocking sclerostin releases a brake on the canonical Wnt/β-catenin signaling in osteoblasts. Sclerostin, produced by osteocytes, binds to LRP5/6 and prevents Wnt ligands from activating the pathway, keeping β-catenin from accumulating. When sclerostin is inhibited, Wnt signaling proceeds through Frizzled/LRP5/6, stabilizes β-catenin, and promotes its entry into the nucleus to drive transcription of osteogenic genes, leading to increased osteoblast activity and bone formation. This makes the Wnt pathway the key route by which osteoblasts are stimulated when sclerostin is blocked. Other pathways may be involved in various cellular processes, but they are not the primary mechanism for this specific effect.