ArticleBone research2023
Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5.
Article in Bone research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 13 citations in OpenAlex.
- Different Lrp5-HBM mutations induce magnitude- and surface-selective effects that are not explained by receptor trafficking.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- The pathogenesis and intersecting mechanisms of monogenic bone mass disorders.Nature reviews. Endocrinology · 2026Review
- Characterising skull pathologies in the Sost-deficient mouse for preclinical evaluation of sclerosteosis treatments.Disease models & mechanisms · 2026Article
- Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Wnt/β-Catenin Pathway and Hydraulic Calcium Silicate-Based Cements: A Narrative Review.Dentistry journal · 2026Review
- Genetic prediction of blood cell reactivity and its potential causal influence on bone continuity and density disorders.Animal models and experimental medicine · 2026Article
- Case Report: Expanding theFrontiers in pediatrics · 2026Article
- Endogenous Osteocyte-Osteoclast Signaling Enables Growth Factor-Free Bone Remodeling, Drug Response, and Cancer Invasion in a Nanoscale Calcified Bone-on-a-Chip Model.bioRxiv : the preprint server for biology · 2025Article
- Piezo1-mediated mechanotransduction controls osteocyte maturation and dendrite development via a YAP-CCN-Src signaling axis.Nature communications · 2025Article
- Sclerostin-silenced human umbilical cord mesenchymal stem cells ameliorate bone metabolism in steroid-induced femoral head necrosis.World journal of stem cells · 2025Article
- Plasma proteomic profiles reveal proteins and three characteristic patterns associated with osteoporosis: A prospective cohort study.Journal of advanced research · 2025Article
- Sclerostin's role in bone-muscle crosstalk and osteoporosis pathogenesis.Osteoporosis and sarcopenia · 2025Review
- Bone and muscle crosstalk in ageing and disease.Nature reviews. Endocrinology · 2025Review
- Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies.Bone research · 2025Article
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Article
- Comparative analysis of vision transformers and convolutional neural networks in osteoporosis detection from X-ray images.Scientific reports · 2024Article
- Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone research · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function in Sost, which models sclerosteosis, and two strains of mice carrying different point mutations in Lrp5 (equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5-6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.
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Registered trials
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.