ArticleNature communications2020
Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Vascular-lymphatic dual circulation in bone health and disease: Mechanistic coupling and translational therapeutics.Journal of orthopaedic translation · 2026Review
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- CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment.Cell and tissue research · 2026Review
- Zinc and metformin co-functionalized polyetheretherketone: A novel dental implant material tailored for the elderly.Journal of advanced research · 2026Article
- Spondin-1 Inhibits Odontoblastic Differentiation of Human Dental Pulp Stem Cells.Biomolecules · 2026Article
- Advancing Biomaterials Evaluation: A Human Quadruple Bone Cell Culture Reveals Molybdenum-Driven Pro-Osteogenic and Anti-osteoclastogenic Responses.ACS applied materials & interfaces · 2026Article
- Mathematical modeling of bone remodeling after surgical menopause.Frontiers in systems biology · 2026Article
- Article
- Article
- Exploring the Bone-Liver Axis: Impact of Acute Ethanol Intoxication on Post-Traumatic Liver Inflammation and Damage Following Femur Fracture.International journal of molecular sciences · 2025Article
- Mapping the sclerostin-LRP4 binding interface identifies critical interaction hotspots in loops 1 and 3 of sclerostin.FEBS letters · 2025Article
- The Relationship between Sclerostin and Kidney Transplantation Mineral Bone Disorders: A Molecule of Controversies.Calcified tissue international · 2024Review
- Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.Nature communications · 2024Article
- Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone research · 2024Review
- Bone-fat linkage via interleukin-11 in response to mechanical loading.Journal of bone and mineral metabolism · 2024Review
- Design principles and therapeutic applications of novel synthetic WNT signaling agonists.iScience · 2024Review
- Cryo-EM structures elucidate the multiligand receptor nature of megalin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Sclerostin as a new target of diabetes-induced osteoporosis.Frontiers in endocrinology · 2024Review
- Article
- Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults.npj aging · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-density lipoprotein receptor-related protein 6 (LRP6) is a coreceptor of the β-catenin-dependent Wnt signaling pathway. The LRP6 ectodomain binds Wnt proteins, as well as Wnt inhibitors such as sclerostin (SOST), which negatively regulates Wnt signaling in osteocytes. Although LRP6 ectodomain 1 (E1) is known to interact with SOST, several unresolved questions remain, such as the reason why SOST binds to LRP6 E1E2 with higher affinity than to the E1 domain alone. Here, we present the crystal structure of the LRP6 E1E2-SOST complex with two interaction sites in tandem. The unexpected additional binding site was identified between the C-terminus of SOST and the LRP6 E2 domain. This interaction was confirmed by in vitro binding and cell-based signaling assays. Its functional significance was further demonstrated in vivo using Xenopus laevis embryos. Our results provide insights into the inhibitory mechanism of SOST on Wnt signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.