ArticleNature medicine2014
Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1.
Article in Nature medicine, 2014. 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 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
- TNALP associated calcium phosphate microdeposition contributes to thoracic aortic dissection susceptibility.Communications biology · 2026Article
- Advancing neurofibromatosis research: a comparative review of animal models and their utility in dissecting the tumor microenvironment.Laboratory animal research · 2026Review
- Neurofibromin in bone disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- MEK inhibitor mirdametinib promotes fracture healing in osteofibrous dysplasia RASopathy.The Journal of clinical investigation · 2026Article
- Molecular Basis of Fracture Pseudarthrosis Associated with Neurofibromatosis Type 1.Journal of the Pediatric Orthopaedic Society of North America · 2025Review
- Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.JCI insight · 2024Article
- Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1.Clinical trials (London, England) · 2024Review
- Molecular Dissection of Somatic Skeletal Disease in Neurofibromatosis Type 1.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.Neuro-oncology · 2022Review
- Article
- Identifying Bone Matrix Impairments in a Mouse Model of Neurofibromatosis Type 1 (NF1) by Clinically Translatable Techniques.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts.Journal of bone metabolism · 2022Article
- Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?Frontiers in pediatrics · 2022Article
- Genotypes and clinical intervention of patients with neurofibromatosis type 1 associated dystrophic scoliosis.Frontiers in pediatrics · 2022Article
- Review
- MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions.Biomarker research · 2021Review
- Effects of resveratrol on the proliferation and osteogenic differentiation of deciduous dental pulp stem cells from neurofibromatosis type 1 patient.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.Nature communications · 2020Article
- A molecular basis for neurofibroma-associated skeletal manifestations in NF1.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy.The Clinical biochemist. Reviews · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Individuals with neurofibromatosis type-1 (NF1) can manifest focal skeletal dysplasias that remain extremely difficult to treat. NF1 is caused by mutations in the NF1 gene, which encodes the RAS GTPase-activating protein neurofibromin. We report here that ablation of Nf1 in bone-forming cells leads to supraphysiologic accumulation of pyrophosphate (PPi), a strong inhibitor of hydroxyapatite formation, and that a chronic extracellular signal-regulated kinase (ERK)-dependent increase in expression of genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank, causes this phenotype. Nf1 ablation also prevents bone morphogenic protein-2-induced osteoprogenitor differentiation and, consequently, expression of alkaline phosphatase and PPi breakdown, further contributing to PPi accumulation. The short stature and impaired bone mineralization and strength in mice lacking Nf1 in osteochondroprogenitors or osteoblasts can be corrected by asfotase-α enzyme therapy aimed at reducing PPi concentration. These results establish neurofibromin as an essential regulator of bone mineralization. They also suggest that altered PPi homeostasis contributes to the skeletal dysplasias associated with NF1 and that some of the NF1 skeletal conditions could be prevented pharmacologically.
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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.