ArticleBone research2025
Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies.
Article in Bone research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Inhibition of cyclin-dependent kinase 8 modulates chondrocyte transition to hypertrophy and provides in vivo protection against spontaneous osteoarthritis.Bone research · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 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
- Review
- Genomic structural equation modeling decodes skeletal aging: novel loci discovery and multisystem genetic crosstalk.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sclerosteosis, an ultra-rare disorder characterised by high bone mass (HBM) and skeletal overgrowth, leads to facial paralysis, hearing loss and raised intracranial pressure, which is currently managed only through high-risk surgery. Sclerosteosis is caused by SOST mutations and loss of functional sclerostin, a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling. Herein, using in vitro and in vivo approaches, we explore whether LGK974, another potent Wnt inhibitor that targets porcupine (PORCN, Wnt-specific acyltransferase), is a promising sclerosteosis therapeutic. In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase (ALP) activity/mineralisation, decreased Wnt/osteoblast marker (Axin2, Runx2 and Ocn) expression, and downregulated ossification and the Wnt signalling pathway, without affecting osteoclast numbers/resorption. To assess in vivo effects, 6-week-old male and female Sost deficient (Sost
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