ArticleThe Journal of clinical investigation2006
Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 133 citations in OpenAlex.
- 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
- Receptor activator of nuclear factor-kappa B ligand-derived microglia healing peptide 1-AcN inhibits osteoarthritis progression in mice.Arthritis research & therapy · 2025Article
- Impaired MC3T3-E1 osteoblast differentiation triggered by oncogenic HRAS is rescued by the farnesyltransferase inhibitor Tipifarnib.Scientific reports · 2025Article
- Efficacy of Bisphosphonate in Patients with Neurofibromatosis Type 1.Journal of bone metabolism · 2025Article
- Potential endpoints for assessment of bone health in persons with neurofibromatosis type 1.Clinical trials (London, England) · 2024Review
- 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
- Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).PloS one · 2024Article
- Questions about Using the Induced Membrane Technique to Manage Cases of Congenital Tibial Pseudarthrosis.Cells · 2023Article
- Chalcone T4 Inhibits RANKL-Induced Osteoclastogenesis and Stimulates Osteogenesis In Vitro.International journal of molecular sciences · 2023Article
- Low Bone Mass and Recurrent Fractures in Neurofibromatosis With Concomitant Hemoglobin SC Disease.Cureus · 2023Article
- Prophylactic effects of cucurbitacin B in the EAE Model of multiple sclerosis by adjustment of STAT3/IL-23/IL-17 axis and improvement of neuropsychological symptoms.Metabolic brain disease · 2022Article
- Bone densitometry measurements in children with neurofibromatosis Type 1 using quantitative computed tomography.Singapore medical journal · 2022Article
- LY450139 Inhibited Ti-Particle-Induced Bone Dissolution via Suppressing Notch and NF-κB Signaling Pathways.Calcified tissue international · 2022Article
- Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity.Scientific reports · 2022Article
- Current Aspects on the Pathophysiology of Bone Metabolic Defects during Progression of Scoliosis in Neurofibromatosis Type 1.Journal of clinical medicine · 2022Review
- Increased osteoclastogenesis contributes to bone loss in the Costello syndromeFrontiers in cell and developmental biology · 2022Article
- Endocrine system involvement in patients with RASopathies: A case series.Frontiers in endocrinology · 2022Article
- Review
- A novel mutation in NF1 gene of patient with Neurofibromatosis type 1: A case report and functional study.Molecular genetics & genomic medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Individuals with neurofibromatosis type 1 (NF1) have a high incidence of osteoporosis and osteopenia. However, understanding of the cellular and molecular basis of these sequelae is incomplete. Osteoclasts are specialized myeloid cells that are the principal bone-resorbing cells of the skeleton. We found that Nf1(+/-) mice contain elevated numbers of multinucleated osteoclasts. Both osteoclasts and osteoclast progenitors from Nf1(+/-) mice were hyperresponsive to limiting concentrations of M-CSF and receptor activator of NF-kappaB ligand (RANKL) levels. M-CSF-stimulated p21(ras)-GTP and Akt phosphorylation was elevated in Nf1(+/-) osteoclasts associated with gains of function in survival, proliferation, migration, adhesion, and lytic activity. These gains of function are associated with more severe bone loss following ovariectomy as compared with that in syngeneic WT mice. Intercrossing Nf1(+/-) mice and mice deficient in class 1(A) PI3K (p85alpha) restored elevated PI3K activity and Nf1(+/-) osteoclast functions to WT levels. Furthermore, in vitro-differentiated osteoclasts from NF1 patients also displayed elevated Ras/PI3K activity and increased lytic activity analogous to those in murine Nf1(+/-) osteoclasts. Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease.
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