Sclerostin (SOST) (SOST)

Sclerostin is a secreted glycoprotein primarily produced by osteocytes that acts as a potent negative regulator of bone formation [1, 4]. It functions by binding to the LRP5 and LRP6 co-receptors on the surface of osteoblasts, thereby inhibiting the Wnt/beta-catenin signaling pathway [1, 3]. This inhibition leads to reduced osteoblast proliferation and activity, which decreases bone mineral density [3]. In diseases such as osteoporosis, sclerostin serves as a critical therapeutic target [2]. Drugs like romosozumab are designed to bind and neutralize sclerostin, disrupting its interaction with LRP5/6 [2, 4]. This action promotes bone formation and reduces bone resorption, providing a dual-action approach to increasing bone mass and strength in patients at high risk of fracture [2, 3]. References: [1] UniProt (Q9BQB4); [2] FDA Evenity Label (2019); [3] Lim & Bolster, Drug Des Devel Ther (2017); [4] Appelman-Dijkstra & Papapoulos, Calcif Tissue Int (2015).

Other names

SOSTSclerosteosis proteinVBCHBeer-type sclerosteosis protein

Monoclonal antibodies bind to sclerostin, preventing its interaction with LRP5 and LRP6 co-receptors [1, 2]. This neutralization activates the Wnt/beta-catenin signaling pathway, which stimulates osteoblast activity and bone formation while simultaneously reducing bone resorption by affecting osteoclast-regulating factors [2, 3, 4].