ArticleHuman molecular genetics2011
Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Bone Mineral Density in Neurofibromatosis Type 1: A Systematic Review and Meta-Analysis.Calcified tissue international · 2023Pooled it
- 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
- Pharmacological inhibition of RAS pathway alleviates spine deformity in a mouse model of neurofibromatosis type 1.Bone research · 2025Article
- Molecular Basis of Fracture Pseudarthrosis Associated with Neurofibromatosis Type 1.Journal of the Pediatric Orthopaedic Society of North America · 2025Review
- Unraveling neuronal and metabolic alterations in neurofibromatosis type 1.Journal of neurodevelopmental disorders · 2024Review
- Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.JCI insight · 2024Article
- MEK-SHP2 inhibition prevents tibial pseudarthrosis caused byScience translational medicine · 2024Article
- Generation of heterozygous and homozygous NF1 lines from human-induced pluripotent stem cells using CRISPR/Cas9 to investigate bone defects associated with neurofibromatosis type 1.Frontiers in cell and developmental biology · 2024Article
- Review
- Somatic Double Inactivation ofHuman mutation · 2023Article
- 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
- Ablation of the miRNA cluster 24 in cartilage and osteoblasts impairs bone remodeling.Scientific reports · 2022Article
- The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts.Journal of bone metabolism · 2022Article
- Review
- Evaluation of the dimensions, morphology, and position of the mandibular condyles in individuals with neurofibromatosis 1: a case-control study.Clinical oral investigations · 2022Article
- Genotypes and clinical intervention of patients with neurofibromatosis type 1 associated dystrophic scoliosis.Frontiers in pediatrics · 2022Article
- Autophagy is involved in neurofibromatosis type I gene-modulated osteogenic differentiation in human bone mesenchymal stem cells.Experimental and therapeutic medicine · 2021Article
- Review
- Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications.Cancers · 2021Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in NF1 cause neurofibromatosis type I (NF1), a disorder characterized, among other clinical manifestations, by generalized and focal bony lesions. Dystrophic scoliosis and tibial pseudoarthrosis are the most severe skeletal manifestations for which treatment is not satisfactory, emphasizing the dearth of knowledge related to the biology of NF1 in bone cells. Using reporter mice, we report here that the mouse Col2α1-Cre promoter (collagen, type II, alpha 1) is active not only in chondrocytes but also in adult bone marrow osteoprogenitors giving rise to osteoblasts. Based on this finding, we crossed the Col2α1-Cre transgenic and Nf1(flox/flox) mice to determine whether loss of Nf1 in axial and appendicular osteochondroprogenitors recapitulates the skeletal abnormalities of NF1 patients. By microtomographic and X-rays studies, we show that Nf1(Col2)(-/-) mice display progressive scoliosis and kyphosis, tibial bowing and abnormalities in skull and anterior chest wall formation. These defects were accompanied by a low bone mass phenotype, high bone cortical porosity, osteoidosis, increased osteoclastogenesis and decreased osteoblast number, as quantified by histomorphometry and 3D-microtomography. Loss of Nf1 in osteochondroprogenitors also caused severe short stature and intervertebral disc defects. Blockade of the RAS/ERK activation characteristic of Nf1(-/-) osteoprogenitors by lovastatin during embryonic development could attenuate the increased cortical porosity observed in mutant pups. These data and the skeletal similarities between this mouse model and NF1 patients thus suggest that activation of the RAS/ERK pathway by Nf1 loss-of-function in osteochondroprogenitors is responsible for the vertebral and tibia lesions in NF1 patients, and that this molecular signature may represent a good therapeutic target.
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